Functional crosstalk between dendritic cells and Foxp3+ regulatory T cells in the maintenance of immune tolerance

Frontiers in Immunology

Volumn 3, Issue JUN, 2012, Pages 1-10

  Kornete, Mara ^a,b   Piccirillo, Ciriaco A ^a,b  

^a MCGILL UNIVERSITY   (Canada)

^b RESEARCH INSTITUTE OF THE MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

Author keywords

Foxp3; Immunity; Suppression; Tolerance; Tolerogenic DC

Indexed keywords

EID: 84871402588     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2012.00165     Document Type: Article

References (101)

1. Akbari, O., De Kruyff, R. H., and Umetsu, D. T. (2001). Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat. Immunol. 2, 725-731.
2. Akbari, O., Freeman, G. J., Meyer, E. H., Greenfield, E. A., Chang, T. T., Sharpe, A. H., Berry, G., DeKruyff, R. H., and Umetsu, D. T. (2002). Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nat. Med. 8, 1024-1032.
3. Alexander, H, E. (2005). Dendritic cells in tolerance induction. Immunol. Lett. 99, 8-11.
4. Annacker, O., Coombes, J. L., Malmstrom, V., Uhlig, H. H., Bourne, T., Johansson-Lindbom, B., Agace, W. W., Parker, C. M., and Powrie, F. (2005). Essential role for CD103 in the T cell mediated regulation of experimental colitis.J.Exp.Med.202, 1051-1061.
5. Arima,K.,Watanabe,N.,Hanabuchi,S., Chang, M., Sun, S.-C., and Liu, Y.-J. (2010). Distinct signal codes generate dendritic cell functional plasticity. Sci. Signal. 3, ra4.
6. Awasthi, A., Carrier, Y., Peron, J. P. S., Bettelli, E., Kamanaka, M., Flavell, R. A., Kuchroo, V. K., Oukka, M., and Weiner, H. L. (2007). A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat. Immunol. 8, 1380-1389.
7. Baban, B., Chandler, P. R., Sharma, M. D., Pihkala, J., Koni, P. A., Munn, D. H., and Mellor, A. L. (2009). IDO activates regulatory T cells and blocks their conversion into Th17-Like T cells. J. Immunol. 183, 2475-2483.
8. Banchereau, J., and Steinman, R. M. (1998). Dendritic cells and the control of immunity. Nature 392, 245-252.
9. Basu, S., Golovina, T., Mikheeva, T., June, C. H., and Riley, J. L. (2008). Cutting edge: Foxp3mediated induction of pim 2 allows human T regulatory cells to preferentially expand in rapamycin. J. Immunol. 180,5794-5798.
10. Belkaid, Y., and Oldenhove, G. (2008). Tuning microenvironments: induction of regulatory T cells by dendritic cells. Immunity 29,362-371.
11. 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, Xlinked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 27, 20-21.
12. Bettelli, E., Oukka, M., and Kuchroo, V. K. (2007). TH-17 cells in the circle ofimmunityandautoimmunity.Nat. Immunol. 8,345-350.
13. Bluestone, J. A. (2011). Mechanisms of tolerance. Immunol. Rev. 241, 5-19.
14. Bruder, D., Westendorf, A. M., Hansen, W., Prettin, S., Gruber, A. D., Qian, Y., von Boehmer, H., Mahnke, K., and Buer, J. (2005). On the edge of autoimmunity. Diabetes 54, 3395- 3401.
15. Cederbom, L., Hall, H., and Ivars, F. (2000). CD4+CD25+ regulatory T cells down-regulate costimulatory molecules on antigen-presenting cells. Eur. J. Immunol. 30, 1538-1543.
16. Cella, M., Dohring, C., Samaridis, J., Dessing, M., Brockhaus, M., Lanzavecchia, A., and Colonna, M. (1997). A novel inhibitory receptor (ILT3) expressed on monocytes, macrophages, and dendritic cells involved in antigen processing. J. Exp. Med. 185, 1743-1751.
17. Chang, X., Zheng, P., and Liu, Y. (2006). FoxP3:agenetic link between immunodeficiency and autoimmune diseases. Autoimmun. Rev. 5, 399-402.
18. Coombes, J. L., and Powrie, F. (2008). Dendritic cells in intestinal immune regulation. Nat. Rev. Immunol. 8, 435-446.
19. Coombes, J. L., Siddiqui, K. R. R., Arancibia-Cárcamo, 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-β and retinoic acid-dependent mechanism. J. Exp. Med. 204, 1757-1764.
20. d'Hennezel,E.,Ben-Shoshan,M.,Ochs, H. D., Torgerson, T. R., Russell, L. J., Lejtenyi, C., Noya, F. J., Jabado, N., Mazer, B., and Piccirillo, C. A. (2009). FOXP3 forkhead domain mutation and regulatory T cells in the IPEX syndrome. N. Engl. J. Med. 361, 1710-1713.
21. Esplugues, E., Huber, S., Gagliani, N., Hauser, A. E., Town, T., Wan, Y. Y., O'Connor, W., Rongvaux, A., Van Rooijen, N., Haberman, A. M., Iwakura, Y., Kuchroo, V. K., Kolls, J. K., Bluestone, J. A., Herold, K. C., and Flavell, R. A. (2011). Control of TH17 cells occurs in the small intestine. Nature 475,514-518.
22. 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.
23. Ghiringhelli, F. O., Puig, P. E., Roux, S., Parcellier, A., Schmitt, E., Solary, E., Kroemer,G.,Martin,F.O.,Chauffert, B., and Zitvogel, L. (2005). Tumor cells convert immature myeloid dendritic cells into TGF-β secreting cells inducing CD4+CD25+ regulatory T cell proliferation. J. Exp. Med. 202, 919-929.
24. Guiducci, C., Valzasina, B., Dislich, H., and Colombo, M. P. (2005). CD40/CD40L interaction regulates CD4+CD25+ T reg homeostasis through dendritic cell-produced IL-2. Eur. J. Immunol. 35, 557-567.
25. Guilliams, M., Crozat, K., Henri, S., Tamoutounour, S., Grenot, P., Devilard,E.,deBovis,B.A.,Alexopoulou, L., Dalod, M., and Malissen, B. (2010). Skin-draining lymph nodes contain dermis-derived CD103 dendritic cells that constitutively produce retinoic acid and induce Foxp3+ regulatory T cells. Blood. 115, 1958-1968.
26. Hanabuchi, S., Ito, T., Park, W.R., Watanabe, N., Shaw, J. L., Roman, E., Arima, K., Wang, Y.H., Voo, K. S., Cao, W., and Liu, Y.-J. (2010). Thymic stromal lymphopoietin-activated plasmacytoid dendritic cells induce the generation of FOXP3+ regulatory T cells in human thymus. J. Immunol. 184, 2999-3007.
27. Haribhai, D., Williams, J. B., Jia, S., Nickerson, D., Schmitt, E. G., Edwards, B., Ziegelbauer, J., Yassai, M., Li, S.-H., Relland, L. M., Wise, P. M., Chen, A., Zheng, Y.-Q., Simpson, P. M., Gorski, J., Salzman, N. H., Hessner, M. J., Chatila, T. A., and Williams, C. B. (2011). A requisite role for induced regulatory T cells in tolerance based on expanding antigen receptor diversity.Immunity 35, 109-122.
28. Hawiger, D., Inaba, K., Dorsett, Y., Guo, M., Mahnke, K., Rivera, M., Ravetch, J. V., Steinman, R. M., and Nussenzweig, M. C. (2001). Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J. Exp. Med. 194, 769-780.
29. Hawiger, D., Masilamani, R. F., Bettelli, E., Kuchroo, V. K., and Nussenzweig, M. C. (2004). Immunological unresponsiveness characterized by increased expression of CD5 on peripheral T cells induced by dendritic cells in vivo. Immunity 20, 695-705.
30. Hori, S., Nomura, T., and Sakaguchi, S. (2003). Control of regulatory T celldevelopmentbythetranscription factor Foxp3. Science 14, 1057-1061.
31. 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.,andVignali, D. A. A. (2004). Role of LAG-3 in regulatory T cells. Immunity 21, 503-513.
32. Hubert, P., Jacobs, N., Caberg, J.H., Boniver, J., and Delvenne, P. (2007). The cross-talk between dendritic and regulatory T cells: good or evil? J. Leukoc. Biol. 82, 781-794.
33. Igyarto, B. Z., Jenison, M. C., Dudda, J. C., Roers, A., Müller, W., Koni, P. A., Campbell,D.J.,Shlomchik,M.J.,and Kaplan, D. H. (2009). Langerhans cells suppress contact hypersensitivity responses via cognate CD4 interaction and Langerhans cell-derived IL-10. J. Immunol. 183,5085-5093.
34. Iliev, I. D., Matteoli, G., and Rescigno, M. (2007). The yin and yang of intestinal epithelial cells in controlling dendritic cell function. J. Exp. Med. 204,2253-2257.
35. Iliev, I. D., Mileti, E., Matteoli, G., Chieppa, M., and Rescigno, M. (2009). Intestinal epithelial cells promote colitis-protective regulatory Tcell differentiation through dendritic cell conditioning. Mucosal Immunol. 2, 340-350.
36. Ito, T., Yang, M., Wang, Y.-H., Lande, R.,Gregorio,J.,Perng,O. A.,Qin,X.F., Liu, Y.-J., and Gilliet, M. (2007). Plasmacytoid dendritic cells prime IL-10 producing T regulatory cells by inducible costimulator ligand. J. Exp. Med. 204,105-115.
37. Jaensson, E., Uronen-Hansson, H., Pabst, O., Eksteen, B., Tian, J., Coombes, J. L., Berg, P.-L., Davidsson, T., Powrie, F., JohanssonLindbom, B., and Agace, W. W. (2008). Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans. J. Exp. Med. 205,2139-2149.
38. Kryczek, I., Wei, S., Zou, L., Zhu, G., Mottram, P., Xu, H., Chen, L., and Zou, W. (2006). Cutting edge: inductionofB7-H4onAPCsthrough IL-10: novel suppressive mode for regulatory T cells. J. Immunol. 177, 40-44.
39. Kumanogoh, A., Wang, X., Lee, I., Watanabe, C., Kamanaka, M., Shi, W., Yoshida, K., Sato, T., Habu, S., Itoh, M., Sakaguchi, N., Sakaguchi, S., and Kikutani, H. (2001). Increased T cell autoreactivity in the absence of CD40-CD40 ligand interactions: a role of CD40 in regulatory T cell development. J. Immunol. 166, 353-360.
40. Kushwah, R., and Hu, J. (2011). Role of dendritic cells in the induction of regulatory T cells. Cell Biosci. 1,20.
41. Kushwah, R., Wu, J., Oliver, J. R., Jiang, G., Zhang, J., Siminovitch, K. A., and Hu,J. (2010).Uptake of apoptotic DC converts immature DC into tolerogenic DC that induce differentiation of Foxp3+ Treg. Eur. J. Immunol. 40, 1022-1035.
42. Lehuen, A., Diana, J., Zaccone, P., and Cooke, A. (2010). Immune cell crosstalk in type 1 diabetes. Nat. Rev. Immunol. 10, 501-513.
43. 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 gene3 engagement of MHC class II. J. Immunol. 180,5916-5926.
44. Loser, K., Mehling, A., Loeser, S., Apelt, J., Kuhn, A., Grabbe, S., Schwarz, T., Penninger, J. M., and Beissert, S. (2006). Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells. Nat. Med. 12, 1372-1379.
45. Mahnke, K., Guo, M., Lee, S., Sepulveda, H., Swain, S. L., Nussenzweig, M., and Steinman, R. M. (2000). The dendritic cell receptor for endocytosis, Dec-205, can recycle and enhance antigen presentation via major histocompatibility complex class II-positive lysosomal compartments. J. Cell Biol. 151, 673-684.
46. Mahnke, K., Johnson, T. S., Ring, S., and Enk, A. H. (2007). Tolerogenic dendritic cells and regulatory T cells: a two-way relationship. J. Dermatol. Sci. 46,159-167.
47. Mahnke, K., Qian, Y., Knop, J., and Enk, A. H. (2003). Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells.Blood101,4862-4869.
48. Mahnke, K., Schmitt, E., Bonifaz, L., Enk, A. H., and Jonuleit, H. (2002). Immature, but not inactive: the tolerogenic function of immature dendritic cells.Immunol.CellBiol.80, 477-483.
49. Maldonado, R. A., and von Andrian, U. H. (2010). How tolerogenic dendritic cells induce regulatory T cells. Adv. Immunol. 108,111-165.
50. Manavalan, J. S., Rossi, P. C., Vlad, G., Piazza, F., Yarilina, A., Cortesini, R., Mancini, D., and Suciu-Foca, N. (2003). High expression of ILT3 and ILT4 is a general feature of tolerogenic dendritic cells. Transpl. Immunol. 11, 245-258.
51. Manicassamy, S., and Pulendran, B. (2011). Dendritic cell control of tolerogenic responses. Immunol. Rev. 241,206-227.
52. Manicassamy, S., Ravindran, R., Deng, J., Oluoch, H., Denning, T. L., Kasturi, S. P., Rosenthal, K. M., Evavold, B. D.,and Pulendran,B. (2009). Tolllike receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity. Nat. Med. 15, 401-409.
53. Manicassamy, S., Reizis, B., Ravindran, R., Nakaya, H., Salazar-Gonzalez, R. M., Wang, Y.-C., and Pulendran, B. (2010). Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine. Science 329, 849-853.
54. Martin-Gayo, E., Sierra-Filardi, E., Corbí, A. L., and Toribio, M. L. (2010). Plasmacytoid dendritic cells resident in human thymus drive natural Treg cell development. Blood 115, 5366-5375.
55. Matteoli, G., Mazzini, E., Iliev, I. D., Mileti, E., Fallarino, F., Puccetti, P., Chieppa, M., and Rescigno, M. (2010). Gut CD103+ dendritic cells express indoleamine 2,3dioxygenase which influences T regulatory/T effector cell balance and oral tolerance induction. Gut 59, 595-604.
56. Mellor, A. L., Chandler, P., Baban, B., Hansen, A. M., Marshall, B., Pihkala, J., Waldmann, H., Cobbold, S., Adams, E., and Munn, D. H. (2004). Specific subsets of murine dendritic cells acquire potent T cell regulatory functions following CTLA4-mediated induction of indoleamine 2,3 dioxygenase. Int. Immunol. 16, 1391-1401.
57. Mellor, A. L., and Munn, D. H. (2004). Ido expression by dendritic cells: tolerance and tryptophan catabolism. Nat. Rev. Immunol. 4,762-774.
58. Menges, M., Robner, S., Voigtlander, C., Schindler, H., Kukutsch, N. A., Bogdan, C., Erb, K., Schuler, G., and Lutz, M. B. (2002). Repetitive injections of dendritic cells matured with tumor necrosis factor induce antigen-specific protection of mice from autoimmunity.J.Exp.Med.195, 15-22.
59. Morelli, A. E., and Thomson, A. W. (2007). Tolerogenic dendritic cells and the quest for transplant tolerance. Nat. Rev. Immunol. 7, 610-621.
60. Nguyen, N. T., Kimura, A., Nakahama, T., Chinen, I., Masuda, K., Nohara, K., Fujii-Kuriyama, Y., and Kishimoto, T. (2010). Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via akynurenine-dependentmechanism. Proc. Natl. Acad. Sci. U.S.A. 107, 19961-19966.
61. Oderup, C., Cederbom, L., Makowska, A., Cilio, C. M., and Ivars, F. (2006). Cytotoxic T lymphocyte antigen-4dependent down-modulation of costimulatory molecules on dendritic cellsinCD4+CD25+ regulatory Tcell-mediated suppression.Immunology 118,240-249.
62. 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.
63. Pasare, C., and Medzhitov, R. (2003). Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science 299, 1033-1036.
64. Perruche, S., Zhang, P., Liu, Y., Saas, P., Bluestone, J. A., and Chen, W. (2008). CD3-specific antibodyinduced immune tolerance involves transforming growth factor-[beta] from phagocytes digesting apoptotic T cells. Nat. Med. 14,528-535.
65. Pot, C., Apetoh, L., and Kuchroo, V. K. (2011).Type 1 regulatory T cells (Tr1) in autoimmunity. Semin. Immunol. 23, 202-208.
66. Pot, C., Jin, H., Awasthi, A., Liu, S. M., Lai, C.-Y., Madan, R., Sharpe, A. H., Karp, C. L., Miaw, S.-C., Ho, I.-C., and Kuchroo, V. K. (2009). Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10producing Tr1 cells. J. Immunol. 183, 797-801.
67. Proietto,A.I.,van Dommelen,S.,Zhou, P., Rizzitelli, A., D'Amico, A., Steptoe, R. J., Naik, S. H., Lahoud, M. H., Liu, Y., Zheng, P., Shortman, K., and Wu, L. (2008). Dendritic cells in the thymus contribute to T-regulatory cell induction. Proc. Natl. Acad. Sci. U.S.A. 105, 19869- 19874.
68. Pulendran, B., Tang, H., and Manicassamy, S. (2010). Programming dendritic cells to induce TH2 and tolerogenic responses. Nat. Immunol. 11,647-655.
69. Read, S., Malmstrom, V., and Powrie, F. (2000). Cytotoxic T lymphocyte associated antigen 4 plays an essential role in the function of CD25+CD4+ regulatory cells that control intestinal inflammation. J. Exp. Med. 192, 295-302.
70. Rescigno, M. (2010). Dendritic cells in tolerance induction for the treatment of autoimmune diseases. Eur. J. Immunol. 40, 2119-2123.
71. Rutella, S., Danese, S., and Leone, G. (2006). Tolerogenic dendritic cells: cytokine modulation comes of age. Blood 108, 1435-1440.
72. Sakaguchi, S. (2000). RegulatoryTcells: key controllers of immunologic selftolerance. Cell 101,455-458.
73. 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.
74. Sakaguchi, S., Wing, K., Onishi, Y., Prieto-Martin, P., and Yamaguchi, T. (2009). Regulatory T cells: how do they suppress immune responses? Int. Immunol. 21, 1105-1111.
75. Salomon,B.T.,Lenschow,D.J.,Rhee,L., Ashourian, N., Singh, B., Sharpe, A., and Bluestone,J.A. (2000). B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 12,431-440.
76. Sarris, M., Andersen, K. G., Randow, F., Mayr, L., and Betz, A. G. (2008). Neuropilin-1 expression on regulatory T cells enhances their interactions with dendritic cells during antigen recognition. Immunity 28, 402-413.
77. Sgouroudis, E., Kornete, M., and Piccirillo, C. A. (2011). IL-2 production by dendritic cells promotes Foxp3+ regulatory T-cell expansion in autoimmune-resistant NOD congenic mice. Autoimmunity 44, 406-414.
78. Shortman, K., and Naik, S. H. (2007). Steady-state and inflammatory dendritic-celldevelopment. Nat. Rev. Immunol. 7,19-30.
79. Steinman, R. M., Hawiger, D., and Nussenzweig, M. C. (2003). Tolerogenic dendritic cells. Annu. Rev. Immunol. 21, 685-711.
80. Steinman, R. M., and Nussenzweig, M. C. (2002). Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc. Natl. Acad. Sci. U.S.A. 99,351-358.
81. Strauss, L., Whiteside, T. L., Knights, A., Bergmann, C., Knuth, A., and Zippelius, A. (2007). Selective survival of naturally occurring human CD4+CD25+Foxp3+ regulatory T cells cultured with rapamycin. J. Immunol. 178,320-329.
82. 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.
83. Svajger, U., Vidmar, A., and Jeras, M. (2008). Niflumic acid renders dendritic cells tolerogenic and upregulates inhibitory molecules ILT3 and ILT4. Int. Immunopharmacol. 8, 997-1005.
84. 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+ Tcells and dendritic cells in vivo. J. Exp. Med. 203,505-511.
85. Takahashi, T., Kuniyasu, Y., Toda, M., Sakaguchi, N., Itoh, M., Iwata, M., Shimizu, J., and Sakaguchi, S. (1998). Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int. Immunol. 10, 1969-1980.
86. Tang, Q., Adams, J. Y., Tooley, A. J., Bi, M., Fife, B. T., Serra, P., Santamaria, P., Locksley, R. M., Krummel, M. F., and Bluestone, J. A. (2006). Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice. Nat. Immunol. 7, 83-92.
87. Tarbell, K. V., Yamazaki, S., Olson, K., Toy, P., and Steinman, R. M. (2004). CD25+ CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes. J. Exp. Med. 199,1467-1477.
88. Tran, D. Q., Glass, D. D., Uzel, G., Darnell, D. A., Spalding, C., Holland, S. M., and Shevach, E. M. (2009). Analysis of adhesion molecules, target cells, and role of IL-2 in human FOXP3+ regulatory T cell suppressor function. J. Immunol. 182, 2929- 2938.
89. Turnquist, H. R., Raimondi, G., Zahorchak, A. F., Fischer, R. T., Wang, Z., and Thomson, A. W. (2007). Rapamycin-conditioned dendritic cells are poor stimulators of allogeneic CD4+ T cells, but enrich for antigen-specific Foxp3+ T regulatory cells and promote organ transplant tolerance. J. Immunol. 178, 7018-7031.
90. Ueno, H., Klechevsky, E., Morita, R., Aspord, C., Cao, T., Matsui, T., Di Pucchio, T., Connolly, J., Fay, J. W., Pascual, V., Palucka, A. K., and Banchereau, J. (2007). Dendritic cell subsets in health and disease. Immunol. Rev. 219, 118-142.
91. Vremec, D., Pooley, J., Hochrein, H., Wu, L., and Shortman, K. (2000). CD4 and CD8 expression by dendritic cell subtypes in mouse thymus and spleen. J. Immunol. 164, 2978-2986.
92. Wakkach, A., Fournier, N., Brun, V. R., Breittmayer, J.-P., Cottrez, F. O., and Groux, H. (2003). Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo. Immunity 18, 605-617.
93. Watanabe, N., Wang, Y.-H., Lee, H. K., Ito, T., Wang, Y.-H., Cao, W., and Liu, Y.-J. (2005). Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature 436, 1181- 1185.
94. 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.
95. Wing, K., and Sakaguchi, S. (2010). Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat. Immunol. 11, 7-13.
96. Workman, C. J., and Vignali, D. A. A. (2005). Negative regulation of T cell homeostasis by lymphocyte activation gene-3 (CD223). J. Immunol. 174,688-695.
97. Wu, L., and Shortman, K. (2005). Heterogeneity of thymic dendritic cells. Semin. Immunol. 17,304-312.
98. Yamazaki, S., Dudziak, D., Heidkamp, G. F., Fiorese, C., Bonito, A. J., Inaba, K., Nussenzweig, M. C., and Steinman, R. M. (2008). CD8+CD205+ splenic dendritic cells are specialized to induce Foxp3+ regulatory T cells. J. Immunol. 181,6923-6933.
99. Yamazaki, S., Iyoda, T., Tarbell, K., Olson, K., Velinzon, K., Inaba, K., and Steinman, R. M. (2003). Direct expansion of functional CD25+ CD4+ regulatory T cells by antigenprocessing dendritic cells. J. Exp. Med. 198,235-247.
100. 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 Tcells in aninflammatory milieu. J. Immunol. 185,2675-2679.
101. Ziegler, S. F., and Liu, Y.-J. (2006). Thymic stromal lymphopoietin in normal and pathogenic T cell development and function. Nat. Immunol. 7,709-714.