Naturally occurring regulatory T cells: Markers, mechanisms, and manipulation

FASEB Journal

Volumn 26, Issue 6, 2012, Pages 2253-2276

  Schmetterer, Klaus G ^a   Neunkirchner, Alina ^a,b   Pickl, Winfried F ^a,b  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b INSTITUTE FOR MICROELECTRONICS   (Austria)

Author keywords

FOXP3; Immunomodulation; Tolerance

Indexed keywords

ALPHA INTEGRIN; B7 ANTIGEN; CD3 ANTIGEN; CD39 ANTIGEN; CD86 ANTIGEN; CHEMOKINE RECEPTOR CCR6; CYTOKINE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GALECTIN 1; GRANZYME B; HERMES ANTIGEN; HLA DR ANTIGEN; INTERLEUKIN 10; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 35; INTERLEUKIN 4; PERFORIN; PROGRAMMED DEATH 1 RECEPTOR; RECOMBINANT TRANSFORMING GROWTH FACTOR BETA; RETINOIC ACID; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3; TRANSCRIPTION FACTOR NFAT; TRANSFORMING GROWTH FACTOR BETA;

ANTIGEN PRESENTING CELL; AUTOIMMUNE DISEASE; AUTOIMMUNE GASTRITIS; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CYTOKINE RELEASE; DENDRITIC CELL; GASTRITIS; GENETIC ENGINEERING; GRAFT VERSUS HOST REACTION; HUMAN; INSULIN DEPENDENT DIABETES MELLITUS; MYASTHENIA GRAVIS; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; RHEUMATOID ARTHRITIS; SYSTEMIC LUPUS ERYTHEMATOSUS; T LYMPHOCYTE ACTIVATION;

ANIMALS; ANTIGEN-PRESENTING CELLS; ANTIGENS, CD; ANTIGENS, CD44; BIOLOGICAL MARKERS; CD4-POSITIVE T-LYMPHOCYTES; CTLA-4 ANTIGEN; CYTOKINES; FORKHEAD TRANSCRIPTION FACTORS; GALECTINS; GENETIC ENGINEERING; GRANZYMES; HUMANS; IKAROS TRANSCRIPTION FACTOR; IMMUNE TOLERANCE; INDOLEAMINE-PYRROLE 2,3,-DIOXYGENASE; INTEGRIN ALPHA CHAINS; INTERLEUKIN-10; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; PERFORIN; T-LYMPHOCYTES, REGULATORY; TRANSFORMING GROWTH FACTOR BETA;

EID: 84861766132     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.11-193672     Document Type: Review

References (272)

1. Nishizuka, Y., and Sakakura, T. (1969) Thymus and reproduction: sex-linked dysgenesia of the gonad after neonatal thymectomy in mice. Science 166, 753-755
2. Sakaguchi, S., Takahashi, T., and Nishizuka, Y. (1982) Study on cellular events in postthymectomy autoimmune oophoritis in mice. I. Requirement of Lyt-1 effector cells for oocytes damage after adoptive transfer. J. Exp. Med. 156, 1565-1576 (Pubitemid 13167405)
3. Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M., and Toda, M. (1995) Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 155, 1151-1164
4. Fontenot, J. D., Gavin, M. A., and Rudensky, A. Y. (2003) Foxp3 programs the development and function of CD4+CD25+regulatory T cells. Nat. Immunol. 4, 330-336 (Pubitemid 36432314)
5. Hori, S., Nomura, T., and Sakaguchi, S. (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057-1061 (Pubitemid 36222930)
6. Khattri, R., Cox, T., Yasayko, S. A., and Ramsdell, F. (2003) An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat. Immunol. 4, 337-342 (Pubitemid 36432315)
7. Itoh, M., Takahashi, T., Sakaguchi, N., Kuniyasu, Y., Shimizu, J., Otsuka, F., and Sakaguchi, S. (1999) Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J. Immunol. 162, 5317-5326 (Pubitemid 29307138)
8. Ng, W. F., Duggan, P. J., Ponchel, F., Matarese, G., Lombardi, G., Edwards, A. D., Isaacs, J. D., and Lechler, R. I. (2001) Human CD4(+)CD25(+) cells: a naturally occurring population of regulatory T cells. Blood 98, 2736-2744
9. Thornton, A. M., and Shevach, E. M. (2000) Suppressor effector function of CD4+CD25+ immunoregulatory T cells is antigen nonspecific. J. Immunol. 164, 183-190 (Pubitemid 30012989)
10. Baecher-Allan, C., and Hafler, D. A. (2006) Human regulatory T cells and their role in autoimmune disease. Immunol. Rev. 212, 203-216 (Pubitemid 44116710)
11. Waldmann, H., Graca, L., Adams, E., Fairchild, P., and Cobbold, S. (2005) Regulatory T cells in transplantation tolerance. Curr. Top. Microbiol. Immunol. 293, 249-264 (Pubitemid 40791232)
12. Larche, M., Akdis, C. A., and Valenta, R. (2006) Immunological mechanisms of allergen-specific immunotherapy. Nat. Rev. Immunol. 6, 761-771 (Pubitemid 44453462)
13. Ozcan, E., Notarangelo, L. D., and Geha, R. S. (2008) Primary immune deficiencies with aberrant IgE production. J. Allergy Clin. Immunol. 122, 1054-1062
14. Baecher-Allan, C., Brown, J. A., Freeman, G. J., and Hafler, D. A. (2001) CD4+CD25high regulatory cells in human peripheral blood. J. Immunol. 167, 1245-1253 (Pubitemid 32703119)
15. Dieckmann, D., Plottner, H., Berchtold, S., Berger, T., and Schuler, G. (2001) Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood. J. Exp. Med. 193, 1303-1310 (Pubitemid 32524780)
16. Thornton, A. M., and Shevach, E. M. (1998) CD4+CD25+immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 188, 287-296 (Pubitemid 28357757)
17. Oberle, N., Eberhardt, N., Falk, C. S., Krammer, P. H., and Suri-Payer, E. (2007) Rapid suppression of cytokine transcription in human CD4+CD25 T cells by CD4+Foxp3+ regulatory T cells: independence of IL-2 consumption, TGF-beta, and various inhibitors of TCR signaling. J. Immunol. 179, 3578-3587
18. Gavin, M. A., Rasmussen, J. P., Fontenot, J. D., Vasta, V., Manganiello, V. C., Beavo, J. A., and Rudensky, A. Y. (2007) Foxp3-dependent programme of regulatory T-cell differentiation. Nature 445, 771-775 (Pubitemid 46279714)
19. Lin, W., Haribhai, D., Relland, L. M., Truong, N., Carlson, M. R., Williams, C. B., and Chatila, T. A. (2007) Regulatory T cell development in the absence of functional Foxp3. Nat. Immunol. 8, 359-368 (Pubitemid 46745411)
20. Yagi, H., Nomura, T., Nakamura, K., Yamazaki, S., Kitawaki, T., Hori, S., Maeda, M., Onodera, M., Uchiyama, T., Fujii, S., and Sakaguchi, S. (2004) Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. Int. Immunol. 16, 1643-1656
21. Zheng, Y., Josefowicz, S. Z., Kas, A., Chu, T. T., Gavin, M. A., and Rudensky, A. Y. (2007) Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature 445, 936-940
22. Bettelli, E., Dastrange, M., and Oukka, M. (2005) Foxp3 interacts with nuclear factor of activated T cells and NF-kappa B to repress cytokine gene expression and effector functions of T helper cells. Proc. Natl. Acad. Sci. U. S. A. 102, 5138-5143
23. Kharbanda, S., Saxena, S., Yoshida, K., Pandey, P., Kaneki, M., Wang, Q., Cheng, K., Chen, Y. N., Campbell, A., Sudha, T., Yuan, Z. M., Narula, J., Weichselbaum, R., Nalin, C., and Kufe, D. (2000) Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in response to DNA damage. J. Biol. Chem. 275, 322-327 (Pubitemid 30038988)
24. Whitmarsh, A. J., and Davis, R. J. (1996) Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J. Mol. Med. (Berl.) 74, 589-607 (Pubitemid 26343761)
25. Wu, Y., Borde, M., Heissmeyer, V., Feuerer, M., Lapan, A. D., Stroud, J. C., Bates, D. L., Guo, L., Han, A., Ziegler, S. F., Mathis, D., Benoist, C., Chen, L., and Rao, A. (2006) FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell 126, 375-387 (Pubitemid 44092960)
26. Haque, R., Lei, F., Xiong, X., Wu, Y., and Song, J. (2010) FoxP3 and Bcl-xL cooperatively promote regulatory T cell persistence and prevention of arthritis development. Arthritis Res. Ther. 12, R66
27. Sharabi, A., and Mozes, E. (2010) Bcl-xL affects the development of functional CD4 Tregs. Arthritis Res. Ther. 12, 405
28. Sharabi, A., Lapter, S., and Mozes, E. (2010) Bcl-xL is required for the development of functional regulatory CD4 cells in lupus-afflicted mice following treatment with a tolerogenic peptide. J. Autoimmun. 34, 87-95
29. Brunkow, M. E., Jeffery, E. W., Hjerrild, K. A., Paeper, B., Clark, L. B., Yasayko, S. A., Wilkinson, J. E., Galas, D., Ziegler, S. F., and Ramsdell, F. (2001) Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat. Genet. 27, 68-73 (Pubitemid 32044521)
30. Bennett, C. L., Christie, J., Ramsdell, F., Brunkow, M. E., Ferguson, P. J., Whitesell, L., Kelly, T. E., Saulsbury, F. T., Chance, P. F., and Ochs, H. D. (2001) The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 27, 20-21 (Pubitemid 32044513)
31. Chatila, T. A., Blaeser, F., Ho, N., Lederman, H. M., Voulgaropoulos, C., Helms, C., and Bowcock, A. M. (2000) JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J. Clin. Invest. 106, R75-81 (Pubitemid 32038594)
32. Wan, Y. Y., and Flavell, R. A. (2007) Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 445, 766-770 (Pubitemid 46279706)
33. Pacholczyk, R., and Kern, J. (2008) The T-cell receptor repertoire of regulatory T cells. Immunology 125, 450-458
34. Ohkura, N., and Sakaguchi, S. (2010) Regulatory T cells: roles of T cell receptor for their development and function. Semin. Immunopathol. 32, 95-106
35. Kuczma, M., Pawlikowska, I., Kopij, M., Podolsky, R., Rempala, G. A., and Kraj, P. (2009) TCR repertoire and Foxp3 expression define functionally distinct subsets of CD4+ regulatory T cells. J. Immunol. 183, 3118-3129
36. Hatakeyama, M., Tsudo, M., Minamoto, S., Kono, T., Doi, T., Miyata, T., Miyasaka, M., and Taniguchi, T. (1989) Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's. Science 244, 551-556 (Pubitemid 19140807)
37. Walker, M. R., Kasprowicz, D. J., Gersuk, V. H., Benard, A., Van Landeghen, M., Buckner, J. H., and Ziegler, S. F. (2003) Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J. Clin. Invest. 112, 1437-1443 (Pubitemid 38057697)
38. Fontenot, J. D., Rasmussen, J. P., Williams, L. M., Dooley, J. L., Farr, A. G., and Rudensky, A. Y. (2005) Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22, 329-341 (Pubitemid 40387475)
39. Takahashi, T., Tagami, T., Yamazaki, S., Uede, T., Shimizu, J., Sakaguchi, N., Mak, T. W., and Sakaguchi, S. (2000) Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med. 192, 303-310
40. McHugh, R. S., Whitters, M. J., Piccirillo, C. A., Young, D. A., Shevach, E. M., Collins, M., and Byrne, M. C. (2002) CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 16, 311-323 (Pubitemid 34211969)
41. Buonavista, N., Balzano, C., Pontarotti, P., Le Paslier, D., and Golstein, P. (1992) Molecular linkage of the human CTLA4 and CD28 Ig-superfamily genes in yeast artificial chromosomes. Genomics 13, 856-861
42. Linsley, P. S., Brady, W., Urnes, M., Grosmaire, L. S., Damle, N. K., and Ledbetter, J. A. (1991) CTLA-4 is a second receptor for the B cell activation antigen B7. J. Exp. Med. 174, 561-569
43. Kanamaru, F., Youngnak, P., Hashiguchi, M., Nishioka, T., Takahashi, T., Sakaguchi, S., Ishikawa, I., and Azuma, M. (2004) Costimulation via glucocorticoid-induced TNF receptor in both conventional and CD25+ regulatory CD4+ T cells. J. Immunol. 172, 7306-7314 (Pubitemid 38747590)
44. Kober, J., Leitner, J., Klauser, C., Woitek, R., Majdic, O., Stockl, J., Herndler-Brandstetter, D., Grubeck-Loebenstein, B., Reipert, B. M., Pickl, W. F., Pfistershammer, K., and Steinberger, P. (2008) The capacity of the TNF family members 4-1BBL, OX40L, CD70, GITRL, CD30L and LIGHT to costimulate human T cells. Eur. J. Immunol. 38, 2678-2688
45. Shimizu, J., Yamazaki, S., Takahashi, T., Ishida, Y., and Sakaguchi, S. (2002) Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat. Immunol. 3, 135-142 (Pubitemid 34141443)
46. Tuyaerts, S., Van Meirvenne, S., Bonehill, A., Heirman, C., Corthals, J., Waldmann, H., Breckpot, K., Thielemans, K., and Aerts, J. L. (2007) Expression of human GITRL on myeloid dendritic cells enhances their immunostimulatory function but does not abrogate the suppressive effect of CD4+CD25+regulatory T cells. J. Leukoc. Biol. 82, 93-105 (Pubitemid 47026420)
47. Linsley, P. S., Greene, J. L., Tan, P., Bradshaw, J., Ledbetter, J. A., Anasetti, C., and Damle, N. K. (1992) Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes. J. Exp. Med. 176, 1595-1604
48. Liu, W., Putnam, A. L., Xu-Yu, Z., Szot, G. L., Lee, M. R., Zhu, S., Gottlieb, P. A., Kapranov, P., Gingeras, T. R., Fazekas de St Groth, B., Clayberger, C., Soper, D. M., Ziegler, S. F., and Bluestone, J. A. (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J. Exp. Med. 203, 1701-1711 (Pubitemid 44036276)
49. Mellor, A. L., and Munn, D. H. (2011) Physiologic control of the functional status of Foxp3+ regulatory T cells. J. Immunol. 186, 4535-4540
50. Fu, S., Yopp, A. C., Mao, X., Chen, D., Zhang, N., Mao, M., Ding, Y., and Bromberg, J. S. (2004) CD4+ CD25+ CD62+T-regulatory cell subset has optimal suppressive and proliferative potential. Am. J. Transplant. 4, 65-78 (Pubitemid 38155491)
51. Szanya, V., Ermann, J., Taylor, C., Holness, C., and Fathman, C. G. (2002) The subpopulation of CD4+CD25+ splenocytes that delays adoptive transfer of diabetes expresses L-selectin and high levels of CCR7. J. Immunol. 169, 2461-2465 (Pubitemid 34920990)
52. Ermann, J., Hoffmann, P., Edinger, M., Dutt, S., Blankenberg, F. G., Higgins, J. P., Negrin, R. S., Fathman, C. G., and Strober, S. (2005) Only the CD62L+ subpopulation of CD4+CD25+regulatory T cells protects from lethal acute GVHD. Blood 105, 2220-2226 (Pubitemid 40731816)
53. Francisco, L. M., Sage, P. T., and Sharpe, A. H. (2010) The PD-1 pathway in tolerance and autoimmunity. Immunol. Rev. 236, 219-242
54. Freeman, G. J., Wherry, E. J., Ahmed, R., and Sharpe, A. H. (2006) Reinvigorating exhausted HIV-specific T cells via PD-1-PD-1 ligand blockade. J. Exp. Med. 203, 2223-2227 (Pubitemid 44498355)
55. Kitazawa, Y., Fujino, M., Wang, Q., Kimura, H., Azuma, M., Kubo, M., Abe, R., and Li, X. K. (2007) Involvement of the programmed death-1/programmed death-1 ligand pathway in CD4+CD25+ regulatory T-cell activity to suppress alloimmune responses. Transplantation 83, 774-782 (Pubitemid 46569197)
56. Raimondi, G., Shufesky, W. J., Tokita, D., Morelli, A. E., and Thomson, A. W. (2006) Regulated compartmentalization of programmed cell death-1 discriminates CD4+CD25+ resting regulatory T cells from activated T cells. J. Immunol. 176, 2808-2816
57. Borsellino, G., Kleinewietfeld, M., Di Mitri, D., Sternjak, A., Diamantini, A., Giometto, R., Hopner, S., Centonze, D., Bernardi, G., Dell'Acqua, M. L., Rossini, P. M., Battistini, L., Rotzschke, O., and Falk, K. (2007) Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood 110, 1225-1232 (Pubitemid 47281420)
58. Deaglio, S., Dwyer, K. M., Gao, W., Friedman, D., Usheva, A., Erat, A., Chen, J. F., Enjyoji, K., Linden, J., Oukka, M., Kuchroo, V. K., Strom, T. B., and Robson, S. C. (2007) Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J. Exp. Med. 204, 1257-1265 (Pubitemid 46919862)
59. Zhou, Q., Yan, J., Putheti, P., Wu, Y., Sun, X., Toxavidis, V., Tigges, J., Kassam, N., Enjyoji, K., Robson, S. C., Strom, T. B., and Gao, W. (2009) Isolated CD39 expression on CD4+ T cells denotes both regulatory and memory populations. Am. J. Transplant. 9, 2303-2311
60. Liu, T., Soong, L., Liu, G., Konig, R., and Chopra, A. K. (2009) CD44 expression positively correlates with Foxp3 expression and suppressive function of CD4+ Treg cells. Biol. Direct 4, 40
61. Baecher-Allan, C., Wolf, E., and Hafler, D. A. (2006) MHC class II expression identifies functionally distinct human regulatory T cells. J. Immunol. 176, 4622-4631
62. Chen, M. L., Yan, B. S., Bando, Y., Kuchroo, V. K., and Weiner, H. L. (2008) Latency-associated peptide identifies a novel CD4+CD25+ regulatory T cell subset with TGFbeta-mediated function and enhanced suppression of experimental autoimmune encephalomyelitis. J. Immunol. 180, 7327-7337
63. Tran, D. Q., Andersson, J., Hardwick, D., Bebris, L., Illei, G. G., and Shevach, E. M. (2009) Selective expression of latency-associated peptide (LAP) and IL-1 receptor type I/II (CD121a/CD121b) on activated human FOXP3+ regulatory T cells allows for their purification from expansion cultures. Blood 113, 5125-5133
64. Suffia, I., Reckling, S. K., Salay, G., and Belkaid, Y. (2005) A role for CD103 in the retention of CD4+CD25+ Treg and control of Leishmania major infection. J. Immunol. 174, 5444-5455 (Pubitemid 40593184)
65. Zhao, D., Zhang, C., Yi, T., Lin, C. L., Todorov, I., Kandeel, F., Forman, S., and Zeng, D. (2008) In vivo-activated CD103+CD4+regulatory T cells ameliorate ongoing chronic graft-versus-host disease. Blood 112, 2129-2138
66. Anz, D., Mueller, W., Golic, M., Kunz, W. G., Rapp, M., Koelzer, V. H., Ellermeier, J., Ellwart, J. W., Schnurr, M., Bourquin, C., and Endres, S. (2011) CD103 is a hallmark of tumor-infiltrating regulatory T cells. Int. J. Cancer 129, 2417-2426
67. Campbell, D. J., and Koch, M. A. (2011) Phenotypical and functional specialization of FOXP3+ regulatory T cells. Nat. Rev. Immunol. 11, 119-130
68. Santodomingo-Garzon, T., Han, J., Le, T., Yang, Y., and Swain, M. G. (2009) Natural killer T cells regulate the homing of chemokine CXC receptor 3-positive regulatory T cells to the liver in mice. Hepatology 49, 1267-1276
69. Hirahara, K., Liu, L., Clark, R. A., Yamanaka, K., Fuhlbrigge, R. C., and Kupper, T. S. (2006) The majority of human peripheral blood CD4+CD25highFoxp3+ regulatory T cells bear functional skin-homing receptors. J. Immunol. 177, 4488-4494 (Pubitemid 44469779)
70. Sather, B. D., Treuting, P., Perdue, N., Miazgowicz, M., Fontenot, J. D., Rudensky, A. Y., and Campbell, D. J. (2007) Altering the distribution of Foxp3(+) regulatory T cells results in tissue-specific inflammatory disease. J. Exp. Med. 204, 1335-1347 (Pubitemid 46919872)
71. Yamazaki, T., Yang, X. O., Chung, Y., Fukunaga, A., Nurieva, R., Pappu, B., Martin-Orozco, N., Kang, H. S., Ma, L., Panopoulos, A. D., Craig, S., Watowich, S. S., Jetten, A. M., Tian, Q., and Dong, C. (2008) CCR6 regulates the migration of inflammatory and regulatory T cells. J. Immunol. 181, 8391-8401
72. Kleinewietfeld, M., Puentes, F., Borsellino, G., Battistini, L., Rotzschke, O., and Falk, K. (2005) CCR6 expression defines regulatory effector/memory-like cells within the CD25(+)CD4+ T-cell subset. Blood 105, 2877-2886 (Pubitemid 40446282)
73. Guo, Z., Jang, M. H., Otani, K., Bai, Z., Umemoto, E., Matsumoto, M., Nishiyama, M., Yamasaki, M., Ueha, S., Matsushima, K., Hirata, T., and Miyasaka, M. (2008) CD4+CD25+ regulatory T cells in the small intestinal lamina propria show an effector/memory phenotype. Int. Immunol. 20, 307-315 (Pubitemid 351321238)
74. Hirota, K., Yoshitomi, H., Hashimoto, M., Maeda, S., Teradaira, S., Sugimoto, N., Yamaguchi, T., Nomura, T., Ito, H., Nakamura, T., Sakaguchi, N., and Sakaguchi, S. (2007) Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model. J. Exp. Med. 204, 2803-2812 (Pubitemid 350179551)
75. Huard, B., Prigent, P., Tournier, M., Bruniquel, D., and Triebel, F. (1995) CD4/major histocompatibility complex class II interaction analyzed with CD4- and lymphocyte activation gene-3 (LAG-3)-Ig fusion proteins. Eur. J. Immunol. 25, 2718-2721
76. Huang, C. T., Workman, C. J., Flies, D., Pan, X., Marson, A. L., Zhou, G., Hipkiss, E. L., Ravi, S., Kowalski, J., Levitsky, H. I., Powell, J. D., Pardoll, D. M., Drake, C. G., and Vignali, D. A. (2004) Role of LAG-3 in regulatory T cells. Immunity 21, 503-513 (Pubitemid 39370506)
77. Tran, D. Q., Andersson, J., Wang, R., Ramsey, H., Unutmaz, D., and Shevach, E. M. (2009) GARP (LRRC32) is essential for the surface expression of latent TGF-beta on platelets and activated FOXP3+ regulatory T cells. Proc. Natl. Acad. Sci. U. S. A. 106, 13445-13450
78. Wang, R., Kozhaya, L., Mercer, F., Khaitan, A., Fujii, H., and Unutmaz, D. (2009) Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells. Proc. Natl. Acad. Sci. U. S. A. 106, 13439-13444
79. Wang, R., Wan, Q., Kozhaya, L., Fujii, H., and Unutmaz, D. (2008) Identification of a regulatory T cell specific cell surface molecule that mediates suppressive signals and induces Foxp3 expression. PLoS One 3, e2705
80. Garin, M. I., Chu, C. C., Golshayan, D., Cernuda-Morollon, E., Wait, R., and Lechler, R. I. (2007) Galectin-1: a key effector of regulation mediated by CD4+CD25+ T cells. Blood 109, 2058-2065 (Pubitemid 46348206)
81. Kubach, J., Lutter, P., Bopp, T., Stoll, S., Becker, C., Huter, E., Richter, C., Weingarten, P., Warger, T., Knop, J., Mullner, S., Wijdenes, J., Schild, H., Schmitt, E., and Jonuleit, H. (2007) Human CD4+CD25+ regulatory T cells: proteome analysis identifies galectin-10 as a novel marker essential for their anergy and suppressive function. Blood 110, 1550-1558 (Pubitemid 47443971)
82. Hill, J. A., Feuerer, M., Tash, K., Haxhinasto, S., Perez, J., Melamed, R., Mathis, D., and Benoist, C. (2007) Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. Immunity 27, 786-800 (Pubitemid 350110546)
83. Sugimoto, N., Oida, T., Hirota, K., Nakamura, K., Nomura, T., Uchiyama, T., and Sakaguchi, S. (2006) Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis. Int. Immunol. 18, 1197-1209 (Pubitemid 44349295)
84. Thornton, A. M., Korty, P. E., Tran, D. Q., Wohlfert, E. A., Murray, P. E., Belkaid, Y., and Shevach, E. M. (2010) Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J. Immunol. 184, 3433-3441
85. Getnet, D., Grosso, J. F., Goldberg, M. V., Harris, T. J., Yen, H. R., Bruno, T. C., Durham, N. M., Hipkiss, E. L., Pyle, K. J., Wada, S., Pan, F., Pardoll, D. M., and Drake, C. G. (2010) A role for the transcription factor Helios in human CD4(+)CD25(+) regulatory T cells. Mol. Immunol. 47, 1595-1600
86. Schreiber, T. H., Wolf, D., Tsai, M. S., Chirinos, J., Deyev, V. V., Gonzalez, L., Malek, T. R., Levy, R. B., and Podack, E. R. (2010) Therapeutic Treg expansion in mice by TNFRSF25 prevents allergic lung inflammation. J. Clin. Invest. 120, 3629-3640
87. Tivol, E. A., Borriello, F., Schweitzer, A. N., Lynch, W. P., Bluestone, J. A., and Sharpe, A. H. (1995) Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 3, 541-547
88. Waterhouse, P., Penninger, J. M., Timms, E., Wakeham, A., Shahinian, A., Lee, K. P., Thompson, C. B., Griesser, H., and Mak, T. W. (1995) Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 270, 985-988
89. Luhder, F., Hoglund, P., Allison, J. P., Benoist, C., and Mathis, D. (1998) Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulates the unfolding of autoimmune diabetes. J. Exp. Med. 187, 427-432 (Pubitemid 28080071)
90. Perrin, P. J., Maldonado, J. H., Davis, T. A., June, C. H., and Racke, M. K. (1996) CTLA-4 blockade enhances clinical disease and cytokine production during experimental allergic encephalomyelitis. J. Immunol. 157, 1333-1336 (Pubitemid 126449068)
91. Leach, D. R., Krummel, M. F., and Allison, J. P. (1996) Enhancement of antitumor immunity by CTLA-4 blockade. Science 271, 1734-1736 (Pubitemid 26102823)
92. Wing, K., Onishi, Y., Prieto-Martin, P., Yamaguchi, T., Miyara, M., Fehervari, Z., Nomura, T., and Sakaguchi, S. (2008) CTLA-4 control over Foxp3+ regulatory T cell function. Science 322, 271-275
93. Paust, S., Lu, L., McCarty, N., and Cantor, H. (2004) Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease. Proc. Natl. Acad. Sci. U. S. A. 101, 10398-10403 (Pubitemid 38924937)
94. Dejean, A. S., Beisner, D. R., Ch'en, I. L., Kerdiles, Y. M., Babour, A., Arden, K. C., Castrillon, D. H., DePinho, R. A., and Hedrick, S. M. (2009) Transcription factor Foxo3 controls the magnitude of T cell immune responses by modulating the function of dendritic cells. Nat. Immunol. 10, 504-513
95. Onishi, Y., Fehervari, Z., Yamaguchi, T., and Sakaguchi, S. (2008) Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation. Proc. Natl. Acad. Sci. U. S. A. 105, 10113-10118
96. Grohmann, U., Orabona, C., Fallarino, F., Vacca, C., Calcinaro, F., Falorni, A., Candeloro, P., Belladonna, M. L., Bianchi, R., Fioretti, M. C., and Puccetti, P. (2002) CTLA-4-Ig regulates tryptophan catabolism in vivo. Nat. Immunol. 3, 1097-1101 (Pubitemid 35363664)
97. Liang, B., Workman, C., Lee, J., Chew, C., Dale, B. M., Colonna, L., Flores, M., Li, N., Schweighoffer, E., Greenberg, S., Tybulewicz, V., Vignali, D., and Clynes, R. (2008) Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II. J. Immunol. 180, 5916-5926
98. Okamura, T., Fujio, K., Shibuya, M., Sumitomo, S., Shoda, H., Sakaguchi, S., and Yamamoto, K. (2009) CD4+CD25-LAG3+regulatory T cells controlled by the transcription factor Egr-2. Proc. Natl. Acad. Sci. U. S. A. 106, 13974-13979
99. Camisaschi, C., Casati, C., Rini, F., Perego, M., De Filippo, A., Triebel, F., Parmiani, G., Belli, F., Rivoltini, L., and Castelli, C. (2010) LAG-3 expression defines a subset of CD4(+)CD25(high)Foxp3(+) regulatory T cells that are expanded at tumor sites. J. Immunol. 184, 6545-6551
100. Hock, B. D., Kato, M., McKenzie, J. L., and Hart, D. N. (2001) A soluble form of CD83 is released from activated dendritic cells and B lymphocytes, and is detectable in normal human sera. Int. Immunol. 13, 959-967 (Pubitemid 32685208)
101. Lechmann, M., Krooshoop, D. J., Dudziak, D., Kremmer, E., Kuhnt, C., Figdor, C. G., Schuler, G., and Steinkasserer, A. (2001) The extracellular domain of CD83 inhibits dendritic cell-mediated T cell stimulation and binds to a ligand on dendritic cells. J. Exp. Med. 194, 1813-1821 (Pubitemid 34028660)
102. Scholler, N., Hayden-Ledbetter, M., Dahlin, A., Hellstrom, I., Hellstrom, K. E., and Ledbetter, J. A. (2002) Cutting edge: CD83 regulates the development of cellular immunity. J. Immunol. 168, 2599-2602 (Pubitemid 34211633)
103. Reinwald, S., Wiethe, C., Westendorf, A. M., Breloer, M., Probst-Kepper, M., Fleischer, B., Steinkasserer, A., Buer, J., and Hansen, W. (2008) CD83 expression in CD4+ T cells modulates inflammation and autoimmunity. J. Immunol. 180, 5890-5897
104. Buelens, C., Verhasselt, V., De Groote, D., Thielemans, K., Goldman, M., and Willems, F. (1997) Human dendritic cell responses to lipopolysaccharide and CD40 ligation are differentially regulated by interleukin-10. Eur. J. Immunol. 27, 1848-1852 (Pubitemid 27345996)
105. Buelens, C., Willems, F., Delvaux, A., Pierard, G., Delville, J. P., Velu, T., and Goldman, M. (1995) Interleukin-10 differentially regulates B7-1 (CD80) and B7-2 (CD86) expression on human peripheral blood dendritic cells. Eur. J. Immunol. 25, 2668-2672
106. Ding, L., Linsley, P. S., Huang, L. Y., Germain, R. N., and Shevach, E. M. (1993) IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the up-regulation of B7 expression. J. Immunol. 151, 1224-1234 (Pubitemid 23219258)
107. Royer, B., Varadaradjalou, S., Saas, P., Guillosson, J. J., Kantelip, J. P., and Arock, M. (2001) Inhibition of IgE-induced activation of human mast cells by IL-10. Clin. Exp. Allergy 31, 694-704 (Pubitemid 32823813)
108. Takanaski, S., Nonaka, R., Xing, Z., O'Byrne, P., Dolovich, J., and Jordana, M. (1994) Interleukin 10 inhibits lipopolysaccharide-induced survival and cytokine production by human peripheral blood eosinophils. J. Exp. Med. 180, 711-715 (Pubitemid 24224150)
109. Taylor, A., Verhagen, J., Akkoc, T., Wenig, R., Flory, E., Blaser, K., Akdis, M., and Akdis, C. A. (2009) IL-10 suppresses CD2-mediated T cell activation via SHP-1. Mol. Immunol. 46, 622-629
110. Kuhn, R., Lohler, J., Rennick, D., Rajewsky, K., and Muller, W. (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75, 263-274 (Pubitemid 23320290)
111. Glocker, E. O., Kotlarz, D., Boztug, K., Gertz, E. M., Schaffer, A. A., Noyan, F., Perro, M., Diestelhorst, J., Allroth, A., Murugan, D., Hatscher, N., Pfeifer, D., Sykora, K. W., Sauer, M., Kreipe, H., Lacher, M., Nustede, R., Woellner, C., Baumann, U., Salzer, U., Koletzko, S., Shah, N., Segal, A. W., Sauerbrey, A., Buderus, S., Snapper, S. B., Grimbacher, B., and Klein, C. (2009) Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N. Engl. J. Med. 361, 2033-2045
112. Jonuleit, H., Schmitt, E., Stassen, M., Tuettenberg, A., Knop, J., and Enk, A. H. (2001) Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood. J. Exp. Med. 193, 1285-1294 (Pubitemid 32524778)
113. Taams, L. S., Smith, J., Rustin, M. H., Salmon, M., Poulter, L. W., and Akbar, A. N. (2001) Human anergic/suppressive CD4(+)CD25(+) T cells: a highly differentiated and apoptosis-prone population. Eur. J. Immunol. 31, 1122-1131
114. Li, M. O., and Flavell, R. A. (2008) TGF-beta: a master of all T cell trades. Cell 134, 392-404
115. Marie, J. C., Letterio, J. J., Gavin, M., and Rudensky, A. Y. (2005) TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells. J. Exp. Med. 201, 1061-1067 (Pubitemid 40524674)
116. Li, M. O., Sanjabi, S., and Flavell, R. A. (2006) Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms. Immunity 25, 455-471 (Pubitemid 44354214)
117. Liu, Y., Zhang, P., Li, J., Kulkarni, A. B., Perruche, S., and Chen, W. (2008) A critical function for TGF-beta signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells. Nat. Immunol. 9, 632-640 (Pubitemid 351712634)
118. Fahlen, L., Read, S., Gorelik, L., Hurst, S. D., Coffman, R. L., Flavell, R. A., and Powrie, F. (2005) T cells that cannot respond to TGF-beta escape control by CD4(+)CD25(+) regulatory T cells. J. Exp. Med. 201, 737-746 (Pubitemid 40395119)
119. Chen, M. L., Pittet, M. J., Gorelik, L., Flavell, R. A., Weissleder, R., von Boehmer, H., and Khazaie, K. (2005) Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo. Proc. Natl. Acad. Sci. U. S. A. 102, 419-424 (Pubitemid 40116782)
120. Green, E. A., Gorelik, L., McGregor, C. M., Tran, E. H., and Flavell, R. A. (2003) CD4+CD25+ T regulatory cells control anti-islet CD8+ T cells through TGF-beta-TGF-beta receptor interactions in type 1 diabetes. Proc. Natl. Acad. Sci. U. S. A. 100, 10878-10883 (Pubitemid 37140121)
121. Nakamura, K., Kitani, A., Fuss, I., Pedersen, A., Harada, N., Nawata, H., and Strober, W. (2004) TGF-beta 1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice. J. Immunol. 172, 834-842 (Pubitemid 38113739)
122. Nakamura, K., Kitani, A., and Strober, W. (2001) Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta. J. Exp. Med. 194, 629-644 (Pubitemid 32844773)
123. Stockis, J., Colau, D., Coulie, P. G., and Lucas, S. (2009) Membrane protein GARP is a receptor for latent TGF-beta on the surface of activated human Treg. Eur. J. Immunol. 39, 3315-3322
124. Collison, L. W., Workman, C. J., Kuo, T. T., Boyd, K., Wang, Y., Vignali, K. M., Cross, R., Sehy, D., Blumberg, R. S., and Vignali, D. A. (2007) The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450, 566-569 (Pubitemid 350190247)
125. Niedbala, W., Wei, X. Q., Cai, B., Hueber, A. J., Leung, B. P., McInnes, I. B., and Liew, F. Y. (2007) IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. Eur. J. Immunol. 37, 3021-3029 (Pubitemid 350131282)
126. Bardel, E., Larousserie, F., Charlot-Rabiega, P., Coulomb-L'Hermine, A., and Devergne, O. (2008) Human CD4+CD25+ Foxp3+ regulatory T cells do not constitutively express IL-35. J. Immunol. 181, 6898-6905
127. Seyerl, M., Kirchberger, S., Majdic, O., Seipelt, J., Jindra, C., Schrauf, C., and Stockl, J. (2010) Human rhinoviruses induce IL-35-producing Treg via induction of B7-H1 (CD274) and sialoadhesin (CD169) on DC. Eur. J. Immunol. 40, 321-329
128. Collison, L. W., Chaturvedi, V., Henderson, A. L., Giacomin, P. R., Guy, C., Bankoti, J., Finkelstein, D., Forbes, K., Workman, C. J., Brown, S. A., Rehg, J. E., Jones, M. L., Ni, H. T., Artis, D., Turk, M. J., and Vignali, D. A. (2010) IL-35-mediated induction of a potent regulatory T cell population. Nat. Immunol. 11, 1093-1101
129. Grossman, W. J., Verbsky, J. W., Barchet, W., Colonna, M., Atkinson, J. P., and Ley, T. J. (2004) Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity 21, 589-601 (Pubitemid 39370513)
130. Gondek, D. C., Lu, L. F., Quezada, S. A., Sakaguchi, S., and Noelle, R. J. (2005) Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. J.
131. Qin, H. Y., Mukherjee, R., Lee-Chan, E., Ewen, C., Bleackley, R. C., and Singh, B. (2006) A novel mechanism of regulatory T cell-mediated down-regulation of autoimmunity. Int. Immunol. 18, 1001-1015 (Pubitemid 43923420)
132. Strauss, L., Bergmann, C., and Whiteside, T. L. (2009) Human circulating CD4+CD25highFoxp3+ regulatory T cells kill autologous CD8+ but not CD4+ responder cells by Fas-mediated apoptosis. J. Immunol. 182, 1469-1480
133. Szymczak-Workman, A. L., Delgoffe, G. M., Green, D. R., and Vignali, D. A. (2011) Cutting edge: Regulatory T cells do not mediate suppression via programmed cell death pathways. J. Immunol. 187, 4416-4420
134. Pandiyan, P., Zheng, L., Ishihara, S., Reed, J., and Lenardo, M. J. (2007) CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat. Immunol. 8, 1353-1362 (Pubitemid 350131172)
135. Kueng, H. J., Manta, C., Haiderer, D., Leb, V. M., Schmetterer, K. G., Neunkirchner, A., Byrne, R. A., Scheinecker, C., Steinberger, P., Seed, B., and Pickl, W. F. (2010) Fluorosomes: a convenient new reagent to detect and block multivalent and complex receptor-ligand interactions. FASEB J. 24, 1572-1582
136. Huang, S., Apasov, S., Koshiba, M., and Sitkovsky, M. (1997) Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion. Blood 90, 1600-1610 (Pubitemid 27355433)
137. Ohta, A., Gorelik, E., Prasad, S. J., Ronchese, F., Lukashev, D., Wong, M. K., Huang, X., Caldwell, S., Liu, K., Smith, P., Chen, J. F., Jackson, E. K., Apasov, S., Abrams, S., and Sitkovsky, M. (2006) A2A adenosine receptor protects tumors from antitumor T cells. Proc. Natl. Acad. Sci. U. S. A. 103, 13132-13137 (Pubitemid 44338928)
138. Bopp, T., Becker, C., Klein, M., Klein-Hessling, S., Palmetshofer, A., Serfling, E., Heib, V., Becker, M., Kubach, J., Schmitt, S., Stoll, S., Schild, H., Staege, M. S., Stassen, M., Jonuleit, H., and Schmitt, E. (2007) Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression. J. Exp. Med. 204, 1303-1310 (Pubitemid 46919868)
139. Fallarino, F., Grohmann, U., Hwang, K. W., Orabona, C., Vacca, C., Bianchi, R., Belladonna, M. L., Fioretti, M. C., Alegre, M. L., and Puccetti, P. (2003) Modulation of tryptophan catabolism by regulatory T cells. Nat. Immunol. 4, 1206-1212 (Pubitemid 37547898)
140. Mellor, A. L., Baban, B., Chandler, P., Marshall, B., Jhaver, K., Hansen, A., Koni, P. A., Iwashima, M., and Munn, D. H. (2003) Cutting edge: induced indoleamine 2,3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion. J. Immunol. 171, 1652-1655 (Pubitemid 36966447)
141. Onodera, T., Jang, M. H., Guo, Z., Yamasaki, M., Hirata, T., Bai, Z., Tsuji, N. M., Nagakubo, D., Yoshie, O., Sakaguchi, S., Takikawa, O., and Miyasaka, M. (2009) Constitutive expression of IDO by dendritic cells of mesenteric lymph nodes: functional involvement of the CTLA-4/B7 and CCL22/CCR4 interactions. J. Immunol. 183, 5608-5614
142. Moffett, J. R., and Namboodiri, M. A. (2003) Tryptophan and the immune response. Immunol. Cell Biol. 81, 247-265 (Pubitemid 36904332)
143. Munn, D. H., Shafizadeh, E., Attwood, J. T., Bondarev, I., Pashine, A., and Mellor, A. L. (1999) Inhibition of T cell proliferation by macrophage tryptophan catabolism. J. Exp. Med. 189, 1363-1372 (Pubitemid 29227522)
144. Bilsborough, J., George, T. C., Norment, A., and Viney, J. L. (2003) Mucosal CD8alpha+ DC, with a plasmacytoid phenotype, induce differentiation and support function of T cells with regulatory properties. Immunology 108, 481-492 (Pubitemid 36469686)
145. Mahnke, K., Ring, S., Johnson, T. S., Schallenberg, S., Schonfeld, K., Storn, V., Bedke, T., and Enk, A. H. (2007) Induction of immunosuppressive functions of dendritic cells in vivo by CD4+CD25+ regulatory T cells: role of B7-H3 expression and antigen presentation. Eur. J. Immunol. 37, 2117-2126 (Pubitemid 47250204)
146. Angelini, G., Gardella, S., Ardy, M., Ciriolo, M. R., Filomeni, G., Di Trapani, G., Clarke, F., Sitia, R., and Rubartelli, A. (2002) Antigen-presenting dendritic cells provide the reducing extracellular microenvironment required for T lymphocyte activation. Proc. Natl. Acad. Sci. U. S. A. 99, 1491-1496 (Pubitemid 34136520)
147. Garg, S. K., Yan, Z., Vitvitsky, V., and Banerjee, R. (2011) Differential dependence on cysteine from transsulfuration versus transport during T cell activation. Antioxid. Redox Signal. 15, 39-47
148. Yan, Z., Garg, S. K., Kipnis, J., and Banerjee, R. (2009) Extracellular redox modulation by regulatory T cells. Nat. Chem. Biol. 5, 721-723
149. Yan, Z., Garg, S. K., and Banerjee, R. (2010) Regulatory T cells interfere with glutathione metabolism in dendritic cells and T cells. J. Biol. Chem. 285, 41525-41532
150. Srivastava, M. K., Sinha, P., Clements, V. K., Rodriguez, P., and Ostrand-Rosenberg, S. (2010) Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine. Cancer Res. 70, 68-77
151. Efimova, O., Szankasi, P., and Kelley, T. W. (2011) Ncf1 (p47phox) is essential for direct regulatory T cell mediated suppression of CD4+ effector T cells. PLoS One 6, e16013
152. Stockinger, B., Barthlott, T., and Kassiotis, G. (2001) T cell regulation: a special job or everyone's responsibility? Nat. Immunol. 2, 757-758
153. Tadokoro, C. E., Shakhar, G., Shen, S., Ding, Y., Lino, A. C., Maraver, A., Lafaille, J. J., and Dustin, M. L. (2006) Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo. J. Exp. Med. 203, 505-511
154. Zhang, H., Chua, K. S., Guimond, M., Kapoor, V., Brown, M. V., Fleisher, T. A., Long, L. M., Bernstein, D., Hill, B. J., Douek, D. C., Berzofsky, J. A., Carter, C. S., Read, E. J., Helman, L. J., and Mackall, C. L. (2005) Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat. Med. 11, 1238-1243 (Pubitemid 43093672)
155. Walker, L. S., Chodos, A., Eggena, M., Dooms, H., and Abbas, A. K. (2003) Antigen-dependent proliferation of CD4+CD25+ regulatory T cells in vivo. J. Exp. Med. 198, 249-258 (Pubitemid 36992178)
156. Jiang, S., Camara, N., Lombardi, G., and Lechler, R. I. (2003) Induction of allopeptide-specific human CD4+CD25+ regulatory T cells ex vivo. Blood 102, 2180-2186 (Pubitemid 37122396)
157. Chen, L. C., Delgado, J. C., Jensen, P. E., and Chen, X. (2009) Direct expansion of human allospecific FoxP3+CD4+ regulatory T cells with allogeneic B cells for therapeutic application. J. Immunol. 183, 4094-4102
158. Allan, S. E., Alstad, A. N., Merindol, N., Crellin, N. K., Amendola, M., Bacchetta, R., Naldini, L., Roncarolo, M. G., Soudeyns, H., and Levings, M. K. (2008) Generation of potent and stable human CD4+ T regulatory cells by activation-independent expression of FOXP3. Mol. Ther. 16, 194-202
159. Earle, K. E., Tang, Q., Zhou, X., Liu, W., Zhu, S., Bonyhadi, M. L., and Bluestone, J. A. (2005) In vitro expanded human CD4+CD25+ regulatory T cells suppress effector T cell proliferation. Clin. Immunol. 115, 3-9 (Pubitemid 40616162)
160. Godfrey, W. R., Ge, Y. G., Spoden, D. J., Levine, B. L., June, C. H., Blazar, B. R., and Porter, S. B. (2004) In vitro-expanded human CD4(+)CD25(+) T-regulatory cells can markedly inhibit allogeneic dendritic cell-stimulated MLR cultures. Blood 104, 453-461 (Pubitemid 38900028)
161. Hoffmann, P., Eder, R., Kunz-Schughart, L. A., Andreesen, R., and Edinger, M. (2004) Large-scale in vitro expansion of polyclonal human CD4(+)CD25high regulatory T cells. Blood 104, 895-903 (Pubitemid 38970590)
162. Allan, S. E., Broady, R., Gregori, S., Himmel, M. E., Locke, N., Roncarolo, M. G., Bacchetta, R., and Levings, M. K. (2008) CD4+ T-regulatory cells: toward therapy for human diseases. Immunol. Rev. 223, 391-421 (Pubitemid 351986179)
163. Koenen, H. J., Fasse, E., and Joosten, I. (2003) IL-15 and cognate antigen successfully expand de novo-induced human antigen-specific regulatory CD4+ T cells that require antigen-specific activation for suppression. J. Immunol. 171, 6431-6441 (Pubitemid 37532071)
164. Chen, H. W., Liao, C. H., Ying, C., Chang, C. J., and Lin, C. M. (2006) Ex vivo expansion of dendritic-cell-activated antigen-specific CD4+ T cells with anti-CD3/CD28, interleukin-7, and interleukin-15: potential for adoptive T cell immunotherapy. Clin. Immunol. 119, 21-31 (Pubitemid 43343864)
165. Elpek, K. G., Yolcu, E. S., Franke, D. D., Lacelle, C., Schabowsky, R. H., and Shirwan, H. (2007) Ex vivo expansion of CD4+CD25+FoxP3+ T regulatory cells based on synergy between IL-2 and 4-1BB signaling. J. Immunol. 179, 7295-7304
166. Zhang, P., Gao, F., Wang, Q., Wang, X., Zhu, F., Ma, C., Sun, W., and Zhang, L. (2007) Agonistic anti-4-1BB antibody promotes the expansion of natural regulatory T cells while maintaining Foxp3 expression. Scand. J. Immunol. 66, 435-440 (Pubitemid 47394563)
167. Chen, X., Oppenheim, J. J., Winkler-Pickett, R. T., Ortaldo, J. R., and Howard, O. M. (2006) Glucocorticoid amplifies IL-2-dependent expansion of functional FoxP3(+)CD4(+)CD25(+) T regulatory cells in vivo and enhances their capacity to suppress EAE. Eur. J. Immunol. 36, 2139-2149 (Pubitemid 44251759)
168. Kretschmer, K., Apostolou, I., Hawiger, D., Khazaie, K., Nussenzweig, M. C., and von Boehmer, H. (2005) Inducing and expanding regulatory T cell populations by foreign antigen. Nat. Immunol. 6, 1219-1227 (Pubitemid 43045633)
169. Apostolou, I., and von Boehmer, H. (2004) In vivo instruction of suppressor commitment in naive T cells. J. Exp. Med. 199, 1401-1408 (Pubitemid 38685731)
170. Maldonado, R. A., and von Andrian, U. H. (2010) How tolerogenic dendritic cells induce regulatory T cells. Adv. Immunol. 108, 111-165
171. Unger, W. W., Laban, S., Kleijwegt, F. S., van der Slik, A. R., and Roep, B. O. (2009) Induction of Treg by monocyte-derived DC modulated by vitamin D3 or dexamethasone: differential role for PD-L1. Eur. J. Immunol. 39, 3147-3159
172. Anderson, A. E., Sayers, B. L., Haniffa, M. A., Swan, D. J., Diboll, J., Wang, X. N., Isaacs, J. D., and Hilkens, C. M. (2008) Differential regulation of naive and memory CD4+ T cells by alternatively activated dendritic cells. J. Leukoc. Biol. 84, 124-133 (Pubitemid 351960287)
173. Buckland, M., Jago, C. B., Fazekasova, H., Scott, K., Tan, P. H., George, A. J., Lechler, R., and Lombardi, G. (2006) Aspirin-treated human DCs up-regulate ILT-3 and induce hyporesponsiveness and regulatory activity in responder T cells. Am. J. Transplant. 6, 2046-2059 (Pubitemid 44199539)
174. Iruretagoyena, M. I., Sepulveda, S. E., Lezana, J. P., Hermoso, M., Bronfman, M., Gutierrez, M. A., Jacobelli, S. H., and Kalergis, A. M. (2006) Inhibition of nuclear factor-kappa B enhances the capacity of immature dendritic cells to induce antigen-specific tolerance in experimental autoimmune encephalomyelitis. J. Pharmacol. Exp. Ther. 318, 59-67
175. Gonzalez-Rey, E., Chorny, A., Fernandez-Martin, A., Ganea, D., and Delgado, M. (2006) Vasoactive intestinal peptide generates human tolerogenic dendritic cells that induce CD4 and CD8 regulatory T cells. Blood 107, 3632-3638
176. Rutella, S., Bonanno, G., Procoli, A., Mariotti, A., de Ritis, D. G., Curti, A., Danese, S., Pessina, G., Pandolfi, S., Natoni, F., Di Febo, A., Scambia, G., Manfredini, R., Salati, S., Ferrari, S., Pierelli, L., Leone, G., and Lemoli, R. M. (2006) Hepatocyte growth factor favors monocyte differentiation into regulatory interleukin (IL)-10++IL-12low/neg accessory cells with dendritic-cell features. Blood 108, 218-227 (Pubitemid 43990632)
177. Ristich, V., Liang, S., Zhang, W., Wu, J., and Horuzsko, A. (2005) Tolerization of dendritic cells by HLA-G. Eur. J. Immunol. 35, 1133-1142 (Pubitemid 40542220)
178. Huang, H., Dawicki, W., Zhang, X., Town, J., and Gordon, J. R. (2010) Tolerogenic dendritic cells induce CD4+CD25hiFoxp3+regulatory T cell differentiation from CD4+CD25-/loFoxp3- effector T cells. J. Immunol. 185, 5003-5010
179. Li, X., Yang, A., Huang, H., Zhang, X., Town, J., Davis, B., Cockcroft, D. W., and Gordon, J. R. (2010) Induction of type 2 T helper cell allergen tolerance by IL-10-differentiated regulatory dendritic cells. Am. J. Respir. Cell Mol. Biol. 42, 190-199
180. Torres-Aguilar, H., Aguilar-Ruiz, S. R., Gonzalez-Perez, G., Munguia, R., Bajana, S., Meraz-Rios, M. A., and Sanchez-Torres, C. (2010) Tolerogenic dendritic cells generated with different immunosuppressive cytokines induce antigen-specific anergy and regulatory properties in memory CD4+ T cells. J. Immunol. 184, 1765-1775
181. Sato, K., Yamashita, N., Baba, M., and Matsuyama, T. (2003) Regulatory dendritic cells protect mice from murine acute graft-versus-host disease and leukemia relapse. Immunity 18, 367-379 (Pubitemid 36351516)
182. Zozulya, A. L., Ortler, S., Lee, J., Weidenfeller, C., Sandor, M., Wiendl, H., and Fabry, Z. (2009) Intracerebral dendritic cells critically modulate encephalitogenic versus regulatory immune responses in the CNS. J. Neurosci. 29, 140-152
183. Verginis, P., Li, H. S., and Carayanniotis, G. (2005) Tolerogenic semimature dendritic cells suppress experimental autoimmune thyroiditis by activation of thyroglobulin-specific CD4+CD25+ T cells. J. Immunol. 174, 7433-7439 (Pubitemid 40705715)
184. Penna, G., Roncari, A., Amuchastegui, S., Daniel, K. C., Berti, E., Colonna, M., and Adorini, L. (2005) Expression of the inhibitory receptor ILT3 on dendritic cells is dispensable for induction of CD4+Foxp3+ regulatory T cells by 1,25-dihydroxyvitamin D3. Blood 106, 3490-3497 (Pubitemid 41609185)
185. Zheng, X., Suzuki, M., Ichim, T. E., Zhang, X., Sun, H., Zhu, F., Shunnar, A., Garcia, B., Inman, R. D., and Min, W. (2010) Treatment of autoimmune arthritis using RNA interference-modulated dendritic cells. J. Immunol. 184, 6457-6464
186. Yang, H., Zhang, Y., Wu, M., Li, J., Zhou, W., Li, G., Li, X., Xiao, B., and Christadoss, P. (2010) Suppression of ongoing experimental autoimmune myasthenia gravis by transfer of RelB-silenced bone marrow dentritic cells is associated with a change from a T helper Th17/Th1 to a Th2 and FoxP3+regulatory T-cell profile. Inflamm. Res. 59, 197-205
187. Matsumura, Y., Kobayashi, T., Ichiyama, K., Yoshida, R., Hashimoto, M., Takimoto, T., Tanaka, K., Chinen, T., Shichita, T., Wyss-Coray, T., Sato, K., and Yoshimura, A. (2007) Selective expansion of foxp3-positive regulatory T cells and immunosuppression by suppressors of cytokine signaling 3-deficient dendritic cells. J. Immunol. 179, 2170-2179
188. Henry, E., Desmet, C. J., Garze, V., Fievez, L., Bedoret, D., Heirman, C., Faisca, P., Jaspar, F. J., Gosset, P., Jacquet, A. P., Desmecht, D., Thielemans, K., Lekeux, P., Moser, M., and Bureau, F. (2008) Dendritic cells genetically engineered to express IL-10 induce long-lasting antigen-specific tolerance in experimental asthma. J. Immunol. 181, 7230-7242
189. Lipscomb, M. W., Taylor, J. L., Goldbach, C. J., Watkins, S. C., Wesa, A. K., and Storkus, W. J. (2010) DC expressing transgene Foxp3 are regulatory APC. Eur. J. Immunol. 40, 480-493
190. Joetham, A., Matsubara, S., Okamoto, M., Takeda, K., Miyahara, N., Dakhama, A., and Gelfand, E. W. (2008) Plasticity of regulatory T cells: subversion of suppressive function and conversion to enhancement of lung allergic responses. J. Immunol. 180, 7117-7124
191. Joetham, A., Okamoto, M., Takeda, K., Schedel, M., Ohnishi, H., Dakhama, A., and Gelfand, E. W. (2011) CD8 regulates T regulatory cell production of IL-6 and maintains their suppressive phenotype in allergic lung disease. J. Immunol. 186, 113-120
192. Sharabi, A., and Mozes, E. (2008) The suppression of murine lupus by a tolerogenic peptide involves foxp3-expressing CD8 cells that are required for the optimal induction and function of foxp3-expressing CD4 cells. J. Immunol. 181, 3243-3251
193. Arazi, A., Sharabi, A., Zinger, H., Mozes, E., and Neumann, A. U. (2009) In vivo dynamical interactions between CD4 Tregs, CD8 Tregs and CD4+ CD25- cells in mice. PLoS One 4, e8447
194. Fantini, M. C., Becker, C., Monteleone, G., Pallone, F., Galle, P. R., and Neurath, M. F. (2004) Cutting edge: TGF-beta induces a regulatory phenotype in CD4+CD25- T cells through Foxp3 induction and down-regulation of Smad7. J. Immunol. 172, 5149-5153 (Pubitemid 38542009)
195. Chen, W., Jin, W., Hardegen, N., Lei, K. J., Li, L., Marinos, N., McGrady, G., and Wahl, S. M. (2003) Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J. Exp. Med. 198, 1875-1886 (Pubitemid 38032120)
196. Park, H. B., Paik, D. J., Jang, E., Hong, S., and Youn, J. (2004) Acquisition of anergic and suppressive activities in transforming growth factor-beta-costimulated CD4+CD25- T cells. Int. Immunol. 16, 1203-1213 (Pubitemid 39136737)
197. Weber, S. E., Harbertson, J., Godebu, E., Mros, G. A., Padrick, R. C., Carson, B. D., Ziegler, S. F., and Bradley, L. M. (2006) Adaptive islet-specific regulatory CD4 T cells control autoimmune diabetes and mediate the disappearance of pathogenic Th1 cells in vivo. J. Immunol. 176, 4730-4739
198. Fantini, M. C., Becker, C., Tubbe, I., Nikolaev, A., Lehr, H. A., Galle, P., and Neurath, M. F. (2006) Transforming growth factor beta induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis. Gut 55, 671-680
199. DiPaolo, R. J., Brinster, C., Davidson, T. S., Andersson, J., Glass, D., and Shevach, E. M. (2007) Autoantigen-specific TGFbeta-induced Foxp3+ regulatory T cells prevent autoimmunity by inhibiting dendritic cells from activating autoreactive T cells. J. Immunol. 179, 4685-4693
200. Selvaraj, R. K., and Geiger, T. L. (2008) Mitigation of experimental allergic encephalomyelitis by TGF-beta induced Foxp3+ regulatory T lymphocytes through the induction of anergy and infectious tolerance. J. Immunol. 180, 2830-2838
201. Zheng, S. G., Wang, J. H., Koss, M. N., Quismorio, F., Jr., Gray, J. D., and Horwitz, D. A. (2004) CD4+ and CD8+ regulatory T cells generated ex vivo with IL-2 and TGF-beta suppress a stimulatory graft-versus-host disease with a lupus-like syndrome. J. Immunol. 172, 1531-1539 (Pubitemid 38116797)
202. Su, H., Ye, D. Q., Wang, B. L., Fang, X. H., Chen, J., Wang, Q., Li, W. X., and Zhang, N. (2008) Transforming growth factor-beta1-induced CD4+CD25+ regulatory T cells in vitro reverse and prevent a murine lupus-like syndrome of chronic graft-versus-host disease. Br. J. Dermatol. 158, 1197-1209 (Pubitemid 351692882)
203. Zheng, S. G., Lan, Qin, Wang, Julie, Brand, David, Horwitz, David A., Liu, Zhong-Min, (2011) Therapeutic effects of TGF-induced regulatory T cells on the established autoimmune diseases. Arthritis Rheum. 63, 849
204. Aricha, R., Feferman, T., Fuchs, S., and Souroujon, M. C. (2008) Ex vivo generated regulatory T cells modulate experimental autoimmune myasthenia gravis. J. Immunol. 180, 2132-2139
205. Zheng, S. G., Wang, J., Wang, P., Gray, J. D., and Horwitz, D. A. (2007) IL-2 is essential for TGF-beta to convert naive CD4+CD25- cells to CD25+Foxp3+ regulatory T cells and for expansion of these cells. J. Immunol. 178, 2018-2027 (Pubitemid 46233398)
206. Zheng, S. G., Wang, J. H., Stohl, W., Kim, K. S., Gray, J. D., and Horwitz, D. A. (2006) TGF-beta requires CTLA-4 early after T cell activation to induce FoxP3 and generate adaptive CD4+CD25+ regulatory cells. J. Immunol. 176, 3321-3329 (Pubitemid 43363978)
207. Tran, D. Q., Ramsey, H., and Shevach, E. M. (2007) Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-beta dependent but does not confer a regulatory phenotype. Blood 110, 2983-2990 (Pubitemid 350006952)
208. Rao, P. E., Petrone, A. L., and Ponath, P. D. (2005) Differentiation and expansion of T cells with regulatory function from human peripheral lymphocytes by stimulation in the presence of TGF-{beta}. J. Immunol. 174, 1446-1455
209. Horwitz, D. A., Zheng, S. G., Wang, J., and Gray, J. D. (2008) Critical role of IL-2 and TGF-beta in generation, function and stabilization of Foxp3+CD4+ Treg. Eur. J. Immunol. 38, 912-915
210. Koenen, H. J., Smeets, R. L., Vink, P. M., van Rijssen, E., Boots, A. M., and Joosten, I. (2008) Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing cells. Blood 112, 2340-2352
211. Sun, C. M., Hall, J. A., Blank, R. B., Bouladoux, N., Oukka, M., Mora, J. R., and Belkaid, Y. (2007) Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J. Exp. Med. 204, 1775-1785 (Pubitemid 47236316)
212. Coombes, J. L., Siddiqui, K. R., Arancibia-Carcamo, C. V., Hall, J., Sun, C. M., Belkaid, Y., and Powrie, F. (2007) A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J. Exp. Med. 204, 1757-1764 (Pubitemid 47236314)
213. Xiao, S., Jin, H., Korn, T., Liu, S. M., Oukka, M., Lim, B., and Kuchroo, V. K. (2008) Retinoic acid increases Foxp3+ regulatory T cells and inhibits development of Th17 cells by enhancing TGF-beta-driven Smad3 signaling and inhibiting IL-6 and IL-23 receptor expression. J. Immunol. 181, 2277-2284
214. Benson, M. J., Pino-Lagos, K., Rosemblatt, M., and Noelle, R. J. (2007) All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. J. Exp. Med. 204, 1765-1774 (Pubitemid 47236315)
215. Zhou, X., Kong, N., Wang, J., Fan, H., Zou, H., Horwitz, D., Brand, D., Liu, Z., and Zheng, S. G. (2010) Cutting edge: all-trans retinoic acid sustains the stability and function of natural regulatory T cells in an inflammatory milieu. J. Immunol. 185, 2675-2679
216. Kang, S. G., Lim, H. W., Andrisani, O. M., Broxmeyer, H. E., and Kim, C. H. (2007) Vitamin A metabolites induce gut-homing FoxP3+ regulatory T cells. J. Immunol. 179, 3724-3733
217. Wang, J., Huizinga, T. W., and Toes, R. E. (2009) De novo generation and enhanced suppression of human CD4+CD25+ regulatory T cells by retinoic acid. J. Immunol. 183, 4119-4126
218. Lu, L., Zhou, X., Wang, J., Zheng, S. G., and Horwitz, D. A. (2010) Characterization of protective human CD4CD25 FOXP3 regulatory T cells generated with IL-2, TGF-beta and retinoic acid. PLoS One 5, e15150
219. Maynard, C. L., Hatton, R. D., Helms, W. S., Oliver, J. R., Stephensen, C. B., and Weaver, C. T. (2009) Contrasting roles for all-trans retinoic acid in TGF-beta-mediated induction of Foxp3 and Il10 genes in developing regulatory T cells. J. Exp. Med. 206, 343-357
220. Jeffery, L. E., Burke, F., Mura, M., Zheng, Y., Qureshi, O. S., Hewison, M., Walker, L. S., Lammas, D. A., Raza, K., and Sansom, D. M. (2009) 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J. Immunol. 183, 5458-5467
221. Baeke, F., Korf, H., Overbergh, L., Verstuyf, A., Thorrez, L., Van Lommel, L., Waer, M., Schuit, F., Gysemans, C., and Mathieu, C. (2011) The vitamin D analog, TX527, promotes a human CD4+CD25highCD127low regulatory T cell profile and induces a migratory signature specific for homing to sites of inflammation. J. Immunol. 186, 132-142
222. Sehgal, S. N. (1998) Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin. Biochem. 31, 335-340
223. Battaglia, M., Stabilini, A., and Roncarolo, M. G. (2005) Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood 105, 4743-4748
224. Singh, A. K., Horvath, K. A., and Mohiuddin, M. M. (2009) Rapamycin promotes the enrichment of CD4(+)CD25(hi)FoxP3(+) T regulatory cells from naive CD4(+) T cells of baboon that suppress antiporcine xenogenic response in vitro. Transplant Proc. 41, 418-421
225. Battaglia, M., Stabilini, A., Migliavacca, B., Horejs-Hoeck, J., Kaupper, T., and Roncarolo, M. G. (2006) Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J. Immunol. 177, 8338-8347 (Pubitemid 44893795)
226. Valmori, D., Tosello, V., Souleimanian, N. E., Godefroy, E., Scotto, L., Wang, Y., and Ayyoub, M. (2006) Rapamycin-mediated enrichment of T cells with regulatory activity in stimulated CD4+ T cell cultures is not due to the selective expansion of naturally occurring regulatory T cells but to the induction of regulatory functions in conventional CD4+ T cells. J. Immunol. 177, 944-949 (Pubitemid 44036595)
227. Long, S. A., and Buckner, J. H. (2008) Combination of rapamycin and IL-2 increases de novo induction of human CD4(+)CD25(+)FOXP3(+) T cells. J. Autoimmun. 30, 293-302
228. Beiras-Fernandez, A., Thein, E., and Hammer, C. (2003) Induction of immunosuppression with polyclonal antithymocyte globulins: an overview. Exp. Clin. Transplant 1, 79-84
229. Genestier, L., Fournel, S., Flacher, M., Assossou, O., Revillard, J. P., and Bonnefoy-Berard, N. (1998) Induction of Fas (Apo-1, CD95)-mediated apoptosis of activated lymphocytes by polyclonal antithymocyte globulins. Blood 91, 2360-2368 (Pubitemid 28155510)
230. Lopez, M., Clarkson, M. R., Albin, M., Sayegh, M. H., and Najafian, N. (2006) A novel mechanism of action for antithymocyte globulin: induction of CD4+CD25+Foxp3+ regulatory T cells. J. Am. Soc. Nephrol. 17, 2844-2853 (Pubitemid 44484674)
231. LaCorcia, G., Swistak, M., Lawendowski, C., Duan, S., Weeden, T., Nahill, S., Williams, J. M., and Dzuris, J. L. (2009) Polyclonal rabbit antithymocyte globulin exhibits consistent immunosuppressive capabilities beyond cell depletion. Transplantation 87, 966-974
232. Ruzek, M. C., Waire, J. S., Hopkins, D., Lacorcia, G., Sullivan, J., Roberts, B. L., Richards, S. M., Nahill, S. R., Williams, J. M., Scaria, A., Dzuris, J., Shankara, S., and Garman, R. D. (2008) Characterization of in vitro antimurine thymocyte globulin-induced regulatory T cells that inhibit graft-versus-host disease in vivo. Blood 111, 1726-1734 (Pubitemid 351213465)
233. Broady, R., Yu, J., and Levings, M. K. (2009) ATG-induced expression of FOXP3 in human CD4(+) T cells in vitro is associated with T-cell activation and not the induction of FOXP3(+) T regulatory cells. Blood 114, 5003-5006
234. Popow, I., Leitner, J., Majdic, O., J, J. K., M, D. S., Zlabinger, G. J., and Steinberger, P. (2012) Assessment of batch to batch variation in polyclonal antithymocyte globulin preparations. Transplantation 93, 32-40
235. Feng, X., Kajigaya, S., Solomou, E. E., Keyvanfar, K., Xu, X., Raghavachari, N., Munson, P. J., Herndon, T. M., Chen, J., and Young, N. S. (2008) Rabbit ATG but not horse ATG promotes expansion of functional CD4+CD25highFOXP3+ regulatory T cells in vitro. Blood 111, 3675-3683
236. Delgado, M., Chorny, A., Gonzalez-Rey, E., and Ganea, D. (2005) Vasoactive intestinal peptide generates CD4+CD25+regulatory T cells in vivo. J. Leukoc. Biol. 78, 1327-1338 (Pubitemid 41779239)
237. Fernandez-Martin, A., Gonzalez-Rey, E., Chorny, A., Ganea, D., and Delgado, M. (2006) Vasoactive intestinal peptide induces regulatory T cells during experimental autoimmune encephalomyelitis. Eur. J. Immunol. 36, 318-326 (Pubitemid 43257454)
238. Gonzalez-Rey, E., Fernandez-Martin, A., Chorny, A., and Delgado, M. (2006) Vasoactive intestinal peptide induces CD4+, CD25+ T regulatory cells with therapeutic effect in collagen-induced arthritis. Arthritis Rheum. 54, 864-876
239. Pozo, D., Anderson, P., and Gonzalez-Rey, E. (2009) Induction of alloantigen-specific human T regulatory cells by vasoactive intestinal peptide. J. Immunol. 183, 4346-4359
240. Chiller, J. M., Habicht, G. S., and Weigle, W. O. (1971) Kinetic differences in unresponsiveness of thymus and bone marrow cells. Science 171, 813-815
241. Thorstenson, K. M., and Khoruts, A. (2001) Generation of anergic and potentially immunoregulatory CD25+CD4 T cells in vivo after induction of peripheral tolerance with intravenous or oral antigen. J. Immunol. 167, 188-195 (Pubitemid 32567777)
242. Zhang, X., Izikson, L., Liu, L., and Weiner, H. L. (2001) Activation of CD25(+)CD4(+) regulatory T cells by oral antigen administration. J. Immunol. 167, 4245-4253 (Pubitemid 32954298)
243. Teitelbaum, D., Meshorer, A., Hirshfeld, T., Arnon, R., and Sela, M. (1971) Suppression of experimental allergic encephalomyelitis by a synthetic polypeptide. Eur. J. Immunol. 1, 242-248
244. Neuhaus, O., Farina, C., Yassouridis, A., Wiendl, H., Then Bergh, F., Dose, T., Wekerle, H., and Hohlfeld, R. (2000) Multiple sclerosis: comparison of copolymer-1- reactive T cell lines from treated and untreated subjects reveals cytokine shift from T helper 1 to T helper 2 cells. Proc. Natl. Acad. Sci. U. S. A. 97, 7452-7457 (Pubitemid 30431484)
245. Begum-Haque, S., Sharma, A., Kasper, I. R., Foureau, D. M., Mielcarz, D. W., Haque, A., and Kasper, L. H. (2008) Downregulation of IL-17 and IL-6 in the central nervous system by glatiramer acetate in experimental autoimmune encephalomyelitis. J. Neuroimmunol. 204, 58-65
246. Hong, J., Li, N., Zhang, X., Zheng, B., and Zhang, J. Z. (2005) Induction of CD4+CD25+ regulatory T cells by copolymer-I through activation of transcription factor Foxp3. Proc. Natl. Acad. Sci. U. S. A. 102, 6449-6454 (Pubitemid 40617463)
247. Cui, G., Zhang, Y., Gong, Z., Zhang, J. Z., and Zang, Y. Q. (2009) Induction of CD4+CD25+Foxp3+ regulatory T cell response by glatiramer acetate in type 1 diabetes. Cell Res. 19, 574-583
248. Jee, Y., Piao, W. H., Liu, R., Bai, X. F., Rhodes, S., Rodebaugh, R., Campagnolo, D. I., Shi, F. D., and Vollmer, T. L. (2007) CD4(+)CD25(+) regulatory T cells contribute to the therapeutic effects of glatiramer acetate in experimental autoimmune encephalomyelitis. Clin. Immunol. 125, 34-42 (Pubitemid 47374537)
249. Kang, H. K., Michaels, M. A., Berner, B. R., and Datta, S. K. (2005) Very low-dose tolerance with nucleosomal peptides controls lupus and induces potent regulatory T cell subsets. J. Immunol. 174, 3247-3255 (Pubitemid 40354027)
250. La Cava, A., Ebling, F. M., and Hahn, B. H. (2004) Ig-reactive CD4+CD25+ T cells from tolerized (New Zealand Black x New Zealand White)F1 mice suppress in vitro production of antibodies to DNA. J. Immunol. 173, 3542-3548 (Pubitemid 39142065)
251. Sharabi, A., Zinger, H., Zborowsky, M., Sthoeger, Z. M., and Mozes, E. (2006) A peptide based on the complementarity-determining region 1 of an autoantibody ameliorates lupus by up-regulating CD4+CD25+ cells and TGF-beta. Proc. Natl. Acad. Sci. U. S. A. 103, 8810-8815 (Pubitemid 43878101)
252. Paas-Rozner, M., Sela, M., and Mozes, E. (2003) A dual altered peptide ligand down-regulates myasthenogenic T cell responses by up-regulating CD25- and CTLA-4-expressing CD4+T cells. Proc. Natl. Acad. Sci. U. S. A. 100, 6676-6681 (Pubitemid 36666640)
253. Dominguez Mdel, C., Lorenzo, N., Barbera, A., Darrasse-Jeze, G., Hernandez, M. V., Torres, A., Hernandez, I., Gil, R., Klatzmann, D., and Padron, G. (2011) An altered peptide ligand corresponding to a novel epitope from heat-shock protein 60 induces regulatory T cells and suppresses pathogenic response in an animal model of adjuvant-induced arthritis. Autoimmunity 44, 471-482
254. Bresson, D., Togher, L., Rodrigo, E., Chen, Y., Bluestone, J. A., Herold, K. C., and von Herrath, M. (2006) Anti-CD3 and nasal proinsulin combination therapy enhances remission from recent-onset autoimmune diabetes by inducing Tregs. J. Clin. Invest. 116, 1371-1381
255. Briner, T. J., Kuo, M. C., Keating, K. M., Rogers, B. L., and Greenstein, J. L. (1993) Peripheral T-cell tolerance induced in naive and primed mice by subcutaneous injection of peptides from the major cat allergen Fel d I. Proc. Natl. Acad. Sci. U. S. A. 90, 7608-7612 (Pubitemid 23249999)
256. Moldaver, D., and Larche, M. (2011) Immunotherapy with peptides. Allergy 66, 784-791
257. Alexander, C., Ying, S., A, B. K., and Larche, M. (2005) Fel d 1-derived T cell peptide therapy induces recruitment of CD4+CD25+; CD4+ interferon-gamma+ T helper type 1 cells to sites of allergen-induced late-phase skin reactions in cat-allergic subjects. Clin. Exp. Allergy 35, 52-58 (Pubitemid 40188270)
258. Tarzi, M., Klunker, S., Texier, C., Verhoef, A., Stapel, S. O., Akdis, C. A., Maillere, B., Kay, A. B., and Larche, M. (2006) Induction of interleukin-10 and suppressor of cytokine signalling- 3 gene expression following peptide immunotherapy. Clin. Exp. Allergy 36, 465-474
259. Fellrath, J. M., Kettner, A., Dufour, N., Frigerio, C., Schneeberger, D., Leimgruber, A., Corradin, G., and Spertini, F. (2003) Allergen-specific T-cell tolerance induction with allergen-derived long synthetic peptides: results of a phase I trial. J. Allergy Clin. Immunol. 111, 854-861 (Pubitemid 36470260)
260. Smith, T. R., Alexander, C., Kay, A. B., Larche, M., and Robinson, D. S.
261. Verhoef, A., Alexander, C., Kay, A. B., and Larche, M. (2005) T cell epitope immunotherapy induces a CD4+ T cell population with regulatory activity. PLoS Med. 2, e78
262. Allan, S. E., Passerini, L., Bacchetta, R., Crellin, N., Dai, M., Orban, P. C., Ziegler, S. F., Roncarolo, M. G., and Levings, M. K. (2005) The role of 2 FOXP3 isoforms in the generation of human CD4+ Tregs. J. Clin. Invest. 115, 3276-3284 (Pubitemid 41567592)
263. Aarts-Riemens, T., Emmelot, M. E., Verdonck, L. F., and Mutis, T. (2008) Forced overexpression of either of the two common human Foxp3 isoforms can induce regulatory T cells from CD4(+)CD25(-) cells. Eur. J. Immunol. 38, 1381-1390
264. Mekala, D. J., and Geiger, T. L. (2005) Immunotherapy of autoimmune encephalomyelitis with redirected CD4+CD25+T lymphocytes. Blood 105, 2090-2092 (Pubitemid 40731796)
265. Elinav, E., Adam, N., Waks, T., and Eshhar, Z. (2009) Amelioration of colitis by genetically engineered murine regulatory T cells redirected by antigen-specific chimeric receptor. Gastroenterology 136, 1721-1731
266. Brusko, T. M., Koya, R. C., Zhu, S., Lee, M. R., Putnam, A. L., McClymont, S. A., Nishimura, M. I., Han, S., Chang, L. J., Atkinson, M. A., Ribas, A., and Bluestone, J. A. (2010) Human antigen-specific regulatory T cells generated by T cell receptor gene transfer. PLoS One 5, e11726
267. Hombach, A. A., Kofler, D., Rappl, G., and Abken, H. (2009) Redirecting human CD4+CD25+ regulatory T cells from the peripheral blood with pre-defined target specificity. Gene Ther. 16, 1088-1096
268. Schmetterer, K. G., Haiderer, D., Leb-Reichl, V. M., Neunkirchner, A., Jahn-Schmid, B., Kung, H. J., Schuch, K., Steinberger, P., Bohle, B., and Pickl, W. F. (2011) Bet v 1-specific T-cell receptor/forkhead box protein 3 transgenic T cells suppress Bet v 1-specific T-cell effector function in an activation-dependent manner. J. Allergy Clin. Immunol. 127, 238-245, 245 e231-233
269. Riley, J. L., June, C. H., and Blazar, B. R. (2009) Human T regulatory cell therapy: take a billion or so and call me in the morning. Immunity 30, 656-665
270. Bluestone, J. A. (2005) Regulatory T-cell therapy: is it ready for the clinic? Nat. Rev. Immunol. 5, 343-349
271. Jahn-Schmid, B., Fischer, G. F., Bohle, B., Fae, I., Gadermaier, G., Dedic, A., Ferreira, F., and Ebner, C. (2005) Antigen presentation of the immunodominant T-cell epitope of the major mugwort pollen allergen, Art v 1, is associated with the expression of HLA-DRB1*01. J. Allergy Clin. Immunol. 115, 399-404 (Pubitemid 40215110)
272. Jahn-Schmid, B., Radakovics, A., Luttkopf, D., Scheurer, S., Vieths, S., Ebner, C., and Bohle, B. (2005) Bet v 1142-156 is the dominant T-cell epitope of the major birch pollen allergen and important for cross-reactivity with Bet v 1-related food allergens. J. Allergy Clin. Immunol. 116, 213-219 (Pubitemid 40909770)