Interleukin-10-secreting type 1 regulatory T cells in rodents and humans

Immunological Reviews

Volumn 212, Issue , 2006, Pages 28-50

  Roncarolo, Maria Grazia ^a   Gregori, Silvia ^a   Battaglia, Manuela ^a   Bacchetta, Rosa ^a   Fleischhauer, Katharina ^a   Levings, Megan K ^b  

^a SAN RAFFAELE SCIENTIFIC INSTITUTE   (Italy)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Interleukin 10; Regulatory T cells; Tr1 cells

Indexed keywords

ADENOVIRUS VECTOR; BIOLOGICAL MARKER; CD3 ANTIBODY; CD4 ANTIGEN; CD8ALPHA ANTIGEN; CHEMOKINE RECEPTOR; CHOLERA TOXIN; COLECALCIFEROL; CYCLOPHOSPHAMIDE; CYTOKINE; DEXAMETHASONE; FLUDARABINE; GRASS POLLEN EXTRACT; INTERLEUKIN 10; INTERLEUKIN 15; INTERLEUKIN 2 RECEPTOR ALPHA; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; OVALBUMIN; RAPAMYCIN; TETRAMER; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA;

ACUTE GRAFT VERSUS HOST DISEASE; ADOPTIVE IMMUNOTHERAPY; ALLERGIC ENCEPHALITIS; ALLERGY; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; ANTIGEN EXPRESSION; ANTIGEN SPECIFICITY; AUTOIMMUNITY; CANCER; CANCER IMMUNOTHERAPY; CELIAC DISEASE; CELL PROLIFERATION; CELLULAR IMMUNITY; CHRONIC LYMPHATIC LEUKEMIA; CYTOKINE PRODUCTION; DENDRITIC CELL; DIABETES MELLITUS; DISEASE COURSE; GENE MUTATION; GRAFT REJECTION; GRAFT VERSUS HOST REACTION; HELICOBACTER HEPATICUS; HEMATOLOGIC MALIGNANCY; HISTOCOMPATIBILITY; HUMAN; IMMUNE DEFICIENCY; IMMUNE RESPONSE; IMMUNIZATION; IMMUNOLOGICAL TOLERANCE; IMMUNOREGULATION; IMMUNOSTIMULATION; IMMUNOSUPPRESSIVE TREATMENT; INFECTION; INFLAMMATION; IRRITABLE COLON; MIDDLE CEREBRAL ARTERY OCCLUSION; MUCOSAL IMMUNITY; MYCOBACTERIUM TUBERCULOSIS; MYCOBACTERIUM VACCAE; NONHUMAN; PANCREAS TRANSPLANTATION; PLASMODIUM FALCIPARUM; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REGULATORY T LYMPHOCYTE; RESPIRATORY TRACT INFLAMMATION; REVIEW; T LYMPHOCYTE SUBPOPULATION; THYMUS; TRANSPLANTATION TOLERANCE; TUMOR IMMUNITY;

ANIMALS; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; IMMUNE SYSTEM DISEASES; IMMUNOSUPPRESSION; INTERLEUKIN-10; LYMPHOCYTE ACTIVATION; MICE; T-LYMPHOCYTES, REGULATORY;

EID: 33746338535     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/j.0105-2896.2006.00420.x     Document Type: Review

References (245)

1. Roncarolo MG, Levings MK. The role of different subsets of T regulatory cells in controlling autoimmunity. Curr Opin Immunol 2000;12:676-683.
2. Battaglia M, Gregori S, Bacchetta R, Roncarolo MG. Tr1 cells: from discovery to their clinical application. Semin Immunol 2006;18:120-127.
3. Shevach EM. CD4+ CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol 2002;2:389-400.
4. Wood KJ, Sakaguchi S. Regulatory T cells in transplantation tolerance. Nat Rev Immunol 2003;3:199-210.
5. Levings MK, Roncarolo MG. Phenotypic and functional differences between human CD4+CD25+ and type 1 regulatory T cells. Curr Top Microbiol Immunol 2005;293:303-326.
6. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989;7:145-173.
7. Moore KW, Vieira P, Fiorentino DF, Trounstine ML, Khan TA, Mosmann TR. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science 1990;248:1230-1234.
8. Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001;19:683-765.
9. Groux H, Bigler M, de Vries JE, Roncarolo MG. Inhibitory and stimulatory effects of IL-10 on human CD8+ T cells. J Immunol 1998;160:3188-3193.
10. Asadullah K, Sterry W, Volk HD. Interleukin-10 therapy-review of a new approach. Pharmacol Rev 2003;55:241-269.
11. Schwarz MA, Hamilton LD, Tardelli L, Narula SK, Sullivan LM. Stimulation of cytolytic activity by interleukin-10. J Immunother Emphasis Tumor Immunol 1994;16:95-104.
12. Llorente L, et al. Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. J Exp Med 1995;181:839-844.
13. Llorente L, et al. Dysregulation of interleukin-10 production in relatives of patients with systemic lupus erythematosus. Arthritis Rheum 1997;40:1429-1435.
14. Groux H, et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997;389:737-742.
15. Bacchetta R, et al. Host-reactive CD4+ and CD8+ T cell clones isolated from a human chimera produce IL-5, IL-2, IFN-gamma and granulocyte/macrophage- colony-stimulating factor but not IL-4. J Immunol 1990;144:902-908.
16. O'Garra A, Vieira PL, Vieira P, Goldfeld AE. IL-10-producing and naturally occurring CD4+ Tregs: limiting collateral damage. J Clin Invest 2004;114:1372-1378.
17. Akdis CA, Blesken T, Akdis M, Wuthrich B, Blaser K. Role of interleukin 10 in specific immunotherapy. J Clin Invest 1998;102:98-106.
18. Akbari O, DeKruyff RH, Umetsu DT. Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat Immunol 2001;2:725-731.
19. Akbari O, et al. Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nat Med 2002;8:1024-1032.
20. Boussiotis VA, et al. IL-10-producing T cells suppress immune responses in anergic tuberculosis patients. J Clin Invest 2000;105:1317-1325.
21. Sundstedt A, Hoiden I, Rosendahl A, Kalland T, van Rooijen N, Dohlsten M. Immunoregulatory role of IL-10 during superantigen-induced hyporesponsiveness in vivo. J Immunol 1997;158:180-186.
22. Sundstedt A, O'Neill EJ, Nicolson KS, Wraith DC. Role for IL-10 in suppression mediated by peptide-induced regulatory T cells in vivo. J Immunol 2003;170:1240-1248.
23. Barrat FJ, et al. In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)-and Th2-inducing cytokines. J Exp Med 2002;195:603-616.
24. Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH. Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med 2000;192:1213-1222.
25. Vieira PL, et al. IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells. J Immunol 2004;172:5986-5993.
26. Bacchetta R, et al. High levels of interleukin 10 production in vivo are associated with tolerance in SCID patients transplanted with HLA mismatched hematopoietic stem cells. J Exp Med 1994;179:493-502.
27. Levings MK, Sangregorio R, Galbiati F, Squadrone S, de Waal Malefyt R, Roncarolo MG. IFN-alpha and IL-10 induce the differentiation of human type 1 T regulatory cells. J Immunol 2001;166:5530-5539.
28. Grundstrom S, Cederbom L, Sundstedt A, Scheipers P, Ivars F. Superantigen-induced regulatory T cells display different suppressive functions in the presence or absence of natural CD4+CD25+ regulatory T cells in vivo. J Immunol 2003;170: 5008-5017.
29. Hawrylowicz CM, O'Garra A. Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma. Nat Rev Immunol 2005;5:271-283.
30. Gilliet M, Liu YJ. Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells. J Exp Med 2002;195:695-704.
31. Steinbrink K, Jonuleit H, Muller G, Schuler G, Knop J, Enk AH. Interleukin-10-treated human dendritic cells induce a melanoma-antigen-specific anergy in CD8(+) T cells resulting in a failure to lyse tumor cells. Blood 1999;93:1634-1642.
32. Gregori S, et al. An anti-CD45RO/RB monoclonal antibody modulates T cell responses via induction of apoptosis and generation of regulatory T cells. J Exp Med 2005;201:1293-1305.
33. Anderson PO, et al. IL-2 overcomes the unresponsiveness but fails to reverse the regulatory function of antigen-induced T regulatory cells. J Immunol 2005;174: 310-319.
34. Bacchetta R, Sartirana C, Levings MK, Bordignon C, Narula S, Roncarolo MG. Growth and expansion of human T regulatory type 1 cells are independent from TCR activation but require exogenous cytokines. Eur J Immunol 2002;32:2237-2245.
35. Sebastiani S, et al. Chemokine receptor expression and function in CD4+ T lymphocytes with regulatory activity. J Immunol 2001;166:996-1002.
36. Freeman CM, et al. CCR8 is expressed by antigen-elicited, IL-10-producing CD4+CD25+ T cells, which regulate Th2-mediated granuloma formation in mice. J Immunol 2005;174:1962-1970.
37. Papadakis KA, et al. CC chemokine receptor 9 expression defines a subset of peripheral blood lymphocytes with mucosal T cell phenotype and Th1 or T-regulatory 1 cytokine profile. J Immunol 2003;171:159-165.
38. Groux H. Type 1 T-regulatory cells: their role in the control of immune responses. Transplantation 2003;75:8S-12S.
39. Fontenot JD, Rudensky AY. A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol 2005;6:331-337.
40. Levings MK, Gregori S, Tresoldi E, Cazzaniga S, Bonini C, Roncarolo MG. Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells. Blood 2005;105:1162-1169.
41. Cobbold SP, et al. Regulatory T cells and dendritic cells in transplantation tolerance: molecular markers and mechanisms. Immunol Rev 2003;196:109-124.
42. Tough DF, Sun S, Zhang X, Sprent J. Stimulation of naive and memory T cells by cytokines. Immunol Rev 1999;170:39-47.
43. Ku CC, Murakami M, Sakamoto A, Kappler J, Marrack P. Control of homeostasis of CD8+ memory T cells by opposing cytokines. Science 2000;288:675-678.
44. Veldman C, Hohne A, Dieckmann D, Schuler G, Hertl M. Type I regulatory T cells specific for desmoglein 3 are more frequently detected in healthy individuals than in patients with pemphigus vulgaris. J Immunol 2004;172:6468-6475.
45. Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB. Interleukin-10 and related cytokines and receptors. Annu Rev Immunol 2004;22:929-979.
46. Strobl H, Knapp W. TGF-beta1 regulation of dendritic cells. Microbes Infect 1999;1:1283-1290.
47. Cerwenka A, Swain SL. TGF-beta1: immunosuppressant and viability factor for T lymphocytes. Microbes Infect 1999;1:1291-1296.
48. Cavani A, Nasorri F, Prezzi C, Sebastiani S, Albanesi C, Girolomoni G. Human CD4+ T lymphocytes with remarkable regulatory functions on dendritic cells and nickel-specific Th1 immune responses. J Invest Dermatol 2000;114:295-302.
49. Kemper C, Chan AC, Green JM, Brett KA, Murphy KM, Atkinson JP. Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype. Nature 2003;421:388-392.
50. Grossman WJ, Verbsky JW, Tollefsen BL, Kemper C, Atkinson JP, Ley TJ. Differential expression of granzymes A and B in human cytotoxic lymphocyte subsets and T regulatory cells. Blood 2004;104:2840-2848.
51. Grossman WJ, Verbsky JW, Bardlet W, Colonna M, Atkinson JP, Ley TJ. Human T regulatory cells can use the perform pathway to cause autologous target cell death. Immunity 2004;21:589-601.
52. Sakaguchi S. Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 2004;22:531-562.
53. Shevach EM. Regulatory/suppressor T cells in health and disease. Arthritis Rheum 2004;50:2721-2724.
54. Walker MR, et al. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J Clin Invest 2003;112:1437-1443.
55. Walker MR, Carson BD, Nepom GT, Ziegler SF, Buckner JH. De novo generation of antigen-specific CD4+CD25+ regulatory T cells from human CD4+CD25- cells. Proc Natl Acad Sci USA 2005;102:4103-4108.
56. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. 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 1995;155:1151-1164.
57. Waldmann H, Graca L, Cobbold S, Adams E, Tone M, Tone Y. Regulatory T cells and organ transplantation. Semin Immunol 2004;16:119-126.
58. Levings MK, et al. Human CD25+CD4+ T suppressor cell clones produce transforming growth factor beta, but not interleukin 10, and are distinct from type 1 T regulatory cells. J Exp Med 2002;196:1335-1346.
59. Brunkow ME, et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet 2001;27:68-73.
60. Khattri R, Cox T, Yasayko SA, Ramsdell F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 2003;4:337-342.
61. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003;4:330-336.
62. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003;299:1057-1061.
63. Kasprowicz DJ, Smallwood PS, Tyznik AJ, Ziegler SF. Scurfin (FoxP3) controls T-dependent immune responses in vivo through regulation of CD4+ T cell effector function. J Immunol 2003;171:1216-1223.
64. Ramsdell F. Foxp3 and natural regulatory T cells: key to a cell lineage? Immunity 2003;19:165-168.
65. Oswald-Richter K, et al. HIV infection of naturally occurring and genetically reprogrammed human regulatory T-cells. PLoS Biol 2004;2:E198.
66. Yagi H, et al. Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. Int Immunol 2004;16:1643-1656.
67. Allan SE, et al. The role of 2 FOXP3 isoforms in the generation of human CD4 Tregs. J Clin Invest 2005;115:3276-3284.
68. Ziegler SF. FOXP3: of mice and men. Annu Rev Immunol 2006;24:209-226.
69. Yamagiwa S, Gray JD, Hashimoto S, Horwitz DA. A role for TGF-beta in the generation and expansion of CD4+CD25+ regulatory T cells from human peripheral blood. J Immunol 2001;166:7282-7289.
70. Rao PE, Petrone AL, Ponath PD. Differentiation and expansion of T cells with regulatory function from human peripheral lymphocytes by stimulation in the presence of TGF- {beta}. J Immunol 2005;174:1446-1455.
71. Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 2005;22:329-341.
72. Dieckmann D, Bruett CH, Ploettner H, Lutz MB, Schuler G. Human CD4(+)CD25(+) regulatory, contact-dependent T cells induce interleukin 10-producing, contact-independent type 1-like regulatory T cells. J Exp Med 2002;196:247-253.
73. Jonuleit H, Schmitt E, Stassen M, Tuettenberg A, Knop J, Enk AH. Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood. J Exp Med 2001;193:1285-1294.
74. Belkaid Y. The role of CD4(+)CD25(+) regulatory T cells in Leishmania infection. Expert Opin Biol Ther 2003;3:875-885.
75. Levings MK, Sangregorio R, Roncarolo MG. Human CD25(+)CD4(+) t regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J Exp Med 2001;193:1295-1302.
76. Levings MK, Bacchetta R, Schulz U, Roncarolo MG. The role of IL-10 and TGF-beta in the differentiation and effector function of T regulatory cells. Int Arch Allergy Immunol 2002;129:263-276.
77. Wahl SM, Swisher J, McCartney-Francis N, Chen W. TGF-beta: the perpetrator of Immune suppression by regulatory T cells and suicidal T cells. J Leukoc Biol 2004;76:15-24.
78. Maloy KJ, Salaun L, Cahill R, Dougan G, Saunders NJ, Powrie F. CD4+CD25+ T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms. J Exp Med 2003;197:111-119.
79. Gorelik L, Constant S, Flavell RA. Mechanism of transforming growth factor beta-induced inhibition of T helper type 1 differentiation. J Exp Med 2002;195:1499-1505.
80. Belghith M, Bluestone JA, Barriot S, Megret J, Bach JF, Chatenoud L. TGF-beta-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetes. Nat Med 2003;9:1202-1208.
81. Piccirillo CA, et al. CD4(+)CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsiveness. J Exp Med 2002;196:237-246.
82. Mamura M, et al. CD28 disruption exacerbates inflammation in Tgf-beta1-/- mice: in vivo suppression by CD4+CD25+ regulatory T cells independent of autocrine TGF-beta1. Blood 2004;103:4594-4601.
83. Kullberg MC, et al. TGF-beta1 production by CD4+ CD25+ regulatory T cells is not essential for suppression of intestinal inflammation. Eur J Immunol 2005;35:2886-2895.
84. Marie JC, Letterio JJ, Gavin M, Rudensky AY. TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells. J Exp Med 2005;201:1061-1067.
85. Stassen M, et al. Human CD25+ regulatory T cells: two subsets defined by the integrins alpha 4 beta 7 or alpha 4 beta 1 confer distinct suppressive properties upon CD4+ T helper cells. Eur J Immunol 2004;34:1303-1311.
86. Foussat A, Cottrez F, Brun V, Fournier N, Breittmayer JP, Groux H. A comparative study between T regulatory type 1 and CD4+CD25+ T cells in the control of inflammation. J Immunol 2003;171:5018-5026.
87. Huehn J, Hamann A. Homing to suppress: address codes for Treg migration. Trends Immunol 2005;26:632-636.
88. Hoffmann P, Ermann J, Edinger M. CD4+CD25+ regulatory T cells in hematopoietic stem cell transplantation. Curr Top Microbiol Immunol 2005;293:265-285.
89. Taylor PA, Lees CJ, Blazar BR. The infusion of ex vivo activated and expanded CD4(+)CD25(+) immune regulatory cells inhibits graft-versus-host disease lethality. Blood 2002;99:3493-3499.
90. Godfrey WR, et al. Cord blood CD4(+)CD25(+)-derived T regulatory cell lines express FoxP3 protein and manifest potent suppressor function. Blood 2005;105:750-758.
91. Battaglia M, Stabilini A, Roncarolo MG. Rapamycin selectively expands CD4+CD25+FOXP3+ regulatory T cells. Blood 2005;105:4743-4748.
92. Groux H, Bigler M, de Vries JE, Roncarolo MG. Interleukin-10 induces a long-term antigen-specific anergic state in human CD4+ T cells. J Exp Med 1996;184:19-29.
93. Boussiotis VA, et al. Altered T-cell receptor + CD28-mediated signaling and blocked cell cycle progression in interleukin 10 and transforming growth factor-beta-treated alloreactive T cells that do not induce graft-versus-host disease. Blood 2001;97:565-571.
94. Zeller JC, et al. Induction of CD4+ T cell alloantigen-specific hyporesponsiveness by IL- 10 and TGF-beta. J Immunol 1999;163:3684-3691.
95. Chen ZM, et al. IL-10 and TGF-beta induce alloreactive CD4+CD25- T cells to acquire regulatory cell function. Blood 2003;101:5076-5083.
96. Wakkach A, Cottrez F, Groux H. Differentiation of regulatory T cells 1 is induced by CD2 costimulation. J Immunol 2001;167:3107-3113.
97. Banchereau J, et al. Immunobiology of dendritic cells. Annu Rev Immunol 2000;18:767-811.
98. Smits HH, de Jong EC, Wierenga EA, Kapsenberg ML. Different faces of regulatory DCs in homeostasis and immunity. Trends Immunol 2005;26:123-129.
99. Mahnke K, Schmitt E, Bonifaz L, Enk AH, Jonuleit H. Immature, but not inactive: the tolerogenic function of immature dendritic cells. Immunol Cell Biol 2002;80:477-483.
100. Hawiger D, et al. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med 2001;194:769-779.
101. Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM. Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J Exp Med 2002;196:1627-1638.
102. Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 2001;193:233-238.
103. Mahnke K, Qian Y, Knop J, Enk AH. Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells. Blood 2003;101:4862-4869.
104. Lanzavecchia A, Sallusto F. Regulation of T cell immunity by dendritic cells. Cell 2001;106:263-266.
105. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998;392:245-252.
106. Penna G, Giarratana N, Amuchastegui S, Mariani R, Daniel KC, Adorini L. Manipulating dendritic cells to induce regulatory T cells. Microbes Infect 2005;7:1033-1039.
107. Mahnke K, Enk AH. Dendritic cells: key cells for the induction of regulatory T cells? Curr Top Microbiol Immunol 2005;293:133-150.
108. Battaglia M, Gianfrani C, Gregori S, Roncarolo MG. IL-10-producing T regulatory type 1 cells and oral tolerance. Ann NY Acad Sci 2004;1029:142-153.
109. Adorini L, et al. Dendritic cells as key targets for immunomodulation by Vitamin D receptor ligands. J Steroid Biochem Mol Biol 2004;89-90:437-441.
110. Woltman AM, van Kooten C. Functional modulation of dendritic cells to suppress adaptive immune responses. J Leukoc Biol 2003;73:428-441.
111. Steinbrink K, Wolfl M, Jonuleit H, Knop J, Enk AH. Induction of tolerance by IL-10-treated dendritic cells. J Immunol 1997;159:4772-4780.
112. Steinbrink K, Graulich E, Kubsch S, Knop J, Enk AH. CD4(+) and CD8(+) anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity. Blood 2002;99:2468-2476.
113. Sato K, Yamashita N, Baba M, Matsuyama T. Modified myeloid dendritic cells act as regulatory dendritic cells to induce anergic and regulatory T cells. Blood 2003;101:3581-3589.
114. Carbonneil C, Saidi H, Donkova-Petrini V, Weiss L. Dendritic cells generated in the presence of interferon-alpha stimulate allogeneic CD4+ T-cell proliferation: modulation by autocrine IL-10, enhanced T-cell apoptosis and T regulatory type 1 cells. Int Immunol 2004;16:1037-1052.
115. Menges M, et al. Repetitive injections of dendritic cells matured with tumor necrosis factor alpha induce antigen-specific protection of mice from autoimmunity. J Exp Med 2002;195:15-21.
116. McGuirk P, McCann C, Mills KH. Pathogen-specific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates interleukin 10 production by dendritic cells: a novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis. J Exp Med 2002;195:221-231.
117. Smits HH, et al. Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J Allergy Clin Immunol 2005;115:1260-1267.
118. Takei M, Umeyama A, Arihara S. Epicubenol and Ferruginol induce DC from human monocytes and differentiate IL-10-producing regulatory T cells in vitro. Biochem Biophys Res Commun 2005;337:730-738.
119. Fiore F, et al. Exposure to myeloma cell lysates affects the immune competence of dendritic cells and favors the induction of Tr1-like regulatory T cells. Eur J Immunol 2005;35:1155-1163.
120. Akasaki Y, Liu G, Chung NH, Ehtesham M, Black KL, Yu JS. Induction of a CD4+ T regulatory type 1 response by cyclooxygenase-2-overexpressing glioma. J Immunol 2004;173:4352-4359.
121. Lundqvist A, Palmborg A, Pavlenko M, Levitskaya J, Pisa P. Mature dendritic cells induce tumor-specific type 1 regulatory T cells. J Immunother 2005;28:229-235.
122. Gray CP, Arosio P, Hersey P. Heavy chain ferritin activates regulatory T cells by induction of changes in dendritic cells. Blood 2002;99:3326-3334.
123. Lu L, et al. Genetic engineering of dendritic cells to express immunosuppressive molecules (viral IL-10, TGF-beta, and CTLA4Ig). J Leukoc Biol 1999;66:293-296.
124. Hackstein H, Morelli AE, Thomson AW. Designer dendritic cells for tolerance induction: guided not misguided missiles. Trends Immunol 2001;22:437-442.
125. Penna G, Adorini L. 1 Alpha,25-dihydroxy-vitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 2000;164:2405-2411.
126. Matyszak MK, Citterio S, Rescigno M, Ricciardi-Castagnoli P. Differential effects of corticosteroids during different stages of dendritic cell maturation. Eur J Immunol 2000;30:1233-1242.
127. Greenwald RJ, Freeman GJ, Sharpe AH. The B7 Family Revisited. Annu Rev Immunol 2005;23:515-548.
128. Chang CC, et al. Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat Immunol 2002;3:237-343.
129. Manavalan JS, et al. High expression of ILT3 and ILT4 is a general feature of tolerogenic dendritic cells. Transpl Immunol 2003;11:245-258.
130. Munn DH, et al. Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science 2002;297:1867-1870.
131. Mellor AL, Keskin DB, Johnson T, Chandler P, Munn DH. Cells expressing indoleamine 2,3-dioxygenase inhibit T cell responses. J Immunol 2002;168:3771-3776.
132. Mellor AL, Munn DH. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 2004;4:762-774.
133. Hwu P, Du MX, Lapointe R, Do M, Taylor MW, Young HA. Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation. J Immunol 2000;164:3596-3599.
134. Funeshima N, et al. Inhibition of allogeneic T-cell responses by dendritic cells expressing transduced indoleamine 2,3-dioxygenase. J Gene Med 2004.
135. Grohmann U, et al. CTLA-4-Ig regulates tryptophan catabolism in vivo. Nat Immunol 2002;3:1097-1101.
136. Mellor AL, et al. Cutting edge: induced indoleamine 2,3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion. J Immunol 2003;171:1652-1655.
137. Fallarino F, et al. Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol 2003;4:1206-1212.
138. Maines MD. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 1997;37:517-554.
139. Chauveau C, et al. Heme oxygenase-1 expression inhibits dendritic cell maturation and proinflammatory function but conserves IL-10 expression. Blood 2005;106:1694-1702.
140. Braudeau C, et al. Induction of long-term cardiac allograft survival by heme oxygenase-1 gene transfer. Gene Ther 2004;11:701-710.
141. Lee TS, Chau LY. Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat Med 2002;8:240-246.
142. Zhang YC, et al. Adeno-associated virus-mediated IL-10 gene therapy inhibits diabetes recurrence in syngeneic islet cell transplantation of NOD mice. Diabetes 2003;52:708-716.
143. Kuwana M, Kaburaki J, Wright TM, Kawakami Y, Ikeda Y. Induction of antigen-specific human CD4(+) T cell anergy by peripheral blood DC2 precursors. Eur J Immunol 2001;31:2547-2457.
144. Kuwana M. Induction of anergic and regulatory T cells by plasmacytoid dendritic cells and other dendritic cell subsets. Hum Immunol 2002;63:1156-1163.
145. Bilsborough J, George TC, Norment A, Viney JL. Mucosal CD8alpha+ DC, with a plasmacytoid phenotype, induce differentiation and support function of T cells with regulatory properties. Immunology 2003;108:481-492.
146. Wakkach A, Founder N, Brun V, Breittmayer JP, Cottrez F, Groux H. Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo. Immunity 2003;18:605-617.
147. Asiedu CK, et al. Elevated T Regulatory Cells in Long-Term Stable Transplant Tolerance in Rhesus Macaques Induced by Anti-CD3 Immunotoxin and Deoxyspergualin. J Immunol 2005;175:8060-8068.
148. Battaglia M, et al. Rapamycin and interleukin-10 treatment induces T regulatory type 1 cells that mediate antigen-specific transplantation tolerance. Diabetes 2006;55:40-49.
149. Chatenoud L. CD3-specific antibody-induced active tolerance: from bench to bedside. Nat Rev Immunol 2003;3:123-132.
150. Herold KC, et al. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med 2002;346:1692-1698.
151. Keymeulen B, et al. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med 2005;352:2598-2608.
152. Herold KC, Burton JB, Francois F, Poumian-Ruiz E, Glandt M, Bluestone JA. Activation of human T cells by FcR nonbinding anti-CD3 mAb, hOKT3gammal(Ala-Ala). J Clin Invest 2003;111:409-418.
153. Baker K, Roncarolo M, Peters C, Bigler M, DeFor Ta, Blazar B. High spontaneous IL-10 production in unrelated bone marrow transplant recipients is associated with fewer transplant-related complications and early deaths. Bone Marrow Transplant 1999;23:1123-1129.
154. Holler E, et al. Prognostic significance of increased IL-10 production in patients prior to allogeneic bone marrow transplantation. Bone Marrow Transplant 2000;25:237-241.
155. Weston LE, Geczy AF, Briscoe H. Production of IL-10 by alloreactive sibling donor cells and its influence on the development of acute GVHD. Bone Marrow Transplant 2006;37:207-212.
156. Lin MT, et al. Relation of an interleukin-10 promoter polymorphism to graft-versus-host disease and survival after hematopoietic-cell transplantation. N Engl J Med 2003;349:2201-2210.
157. Lin MT, et al. Genetic variation in the IL-10 pathway modulates severity of acute graft-versus-host disease following hematopoietic cell transplantation: synergism between IL-10 genotype of patient and IL-10 receptor beta genotype of donor. Blood 2005;106:3995-4001.
158. VanBuskirk AM, et al. Human allograft acceptance is associated with immune regulation. J Clin Invest 2000;106:145-155.
159. Kitani A, Chua K, Nakamura K, Strober W. Activated Self-MHC-Reactive T Cells Have the Cytokine Phenotype of Th3/T Regulatory Cell 1 T Cells. J Immunol 2000;165:691-702.
160. Arif S, et al. Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health. J Clin Invest 2004;113:451-463.
161. Yudoh K, Matsuno H, Nakazawa F, Yonezawa T, Kimura T. Reduced expression of the regulatory CD4+ Tcellsubsetis related to Th1/Th2 balance and disease severity in rheumatoid arthritis. Arthritis Rheum 2000;43:617-627.
162. Hall AM, Ward FJ, Vickers MA, Stott LM, Urbaniak SJ, Barker RN. Interleukin-10-mediated regulatory T-cell responses to epitopes on a human red blood cell autoantigen. Blood 2002;100:4529-4536.
163. + T regulatory cells and T regulatory type 1 cells. Diabetes 2006;55:1571-1580.
164. Saloga J, Bellinghausen I, Knop J. Do Tr1 cells play a role in immunotherapy? Int Arch Allergy Immunol 1999;118:210-211.
165. Reefer AJ, et al. A role for IL-10-mediated HLA-DR7-restricted T cell-dependent events in development of the modified Th2 response to cat allergen. J Immunol 2004;172:2763-2772.
166. Akdis M, et al. Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J Exp Med 2004;199:1567-1575.
167. Hawrylowicz C, Richards D, Loke TK, Corrigan C, Lee T. A defect in corticosteroid-induced IL-10 production in T lymphocytes from corticosteroid-resistant asthmatic patients. J Allergy Clin Immunol 2002;109:369-370.
168. Xystrakis E, et al. Reversing the defective induction of IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients. J Clin Invest 2006;116:146-155.
169. Weiner HL. The mucosal milieu creates tolerogenic dendritic cells and T(R)1 and T(H)3 regulatory cells. Nat Immunol 2001;2:671-672.
170. Morrissey PJ, Charrier K, Braddy S, Liggitt D, Watson JD. CD4+ T cells that express high levels of CD45RB induce wasting disease when transferred into congenic severe combined immunodeficient mice. Disease development is prevented by cotransfer of purified CD4+ T cells. J Exp Med 1993;178:237-244.
171. Powrie F, Leach MW, Mauze S, Caddle LB, Coffman RL. Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 seid mice. Int Immunol 1993;5:1461-1471.
172. Kunkel EJ, et al. Lymphocyte CC chemokine: receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity. J Exp Med 2000;192:761-768.
173. Belkaid Y, Rouse BT. Natural regulatory T cells in infectious disease. Nat Immunol 2005;6:353-360.
174. Mills KH, McGuirk P. Antigen-specific regulatory T cells-their induction and role in infection. Semin Immunol 2004;16:107-117.
175. Belkaid Y, Piccirillo CA, Mendez S, Shevach EM, Sacks DL. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 2002;420:502-507.
176. Zuany-Amorim C, et al. Suppression of airway eosinophilia by killed Mycobacterium vaccae- induced allergen-specific regulatory T-cells. Nat Med 2002;8:625-629.
177. Lavelle EC, McNeela E, Armstrong ME, Leavy O, Higgins SC, Mills KH. Cholera toxin promotes the induction of regulatory T cells specific for bystander antigens by modulating dendritic cell activation. J Immunol 2003;171:2384-2392.
178. Lavelle EC, et al. Effects of cholera toxin on innate and adaptive immunity and its application as an immunomodulatory agent. J Leukoc Biol 2004;75:756-763.
179. MacDonald AJ, et al. CD4 T helper type 1 and regulatory T cells induced against the same epitopes on the core protein in hepatitis C virus-infected persons. J Infect Dis 2002;185:720-727.
180. Satoguina J, et al. Antigen-specific T regulatory-1 cells are associated with immunosuppression in a chronic helminth infection (onchocerciasis). Microbes Infect 2002;4:1291-1230.
181. Kullberg MC, et al. Bacteria-triggered CD4(+) T regulatory cells suppress Helicobacter hepaticus-induced colitis. J Exp Med 2002;196:505-515.
182. Coombes JL, Robinson NJ, Maloy KJ, Uhlig HH, Powrie F. Regulatory T cells and intestinal homeostasis. Immunol Rev 2005;204:184-194.
183. Price JD, Schaumburg J, Sandin C, Atkinson JP, Lindahl G, Kemper C. Induction of a regulatory phenotype in human CD4+ T cells by streptococcal M protein. J Immunol 2005;175:677-684.
184. Ross PJ, Lavelle EC, Mills KH, Boyd AP. Adenylate cyclase toxin from
185. Marshall NA, Vickers MA, Barker RN. Regulatory T cells secreting IL-10 dominate the immune response to EBV latent membrane protein 1. J Immunol 2003;170:6183-6189.
186. Marshall NA, et al. Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood 2004;103:1755-1762.
187. Caramalho I, Lopes-Carvalho T, Ostler D, Zelenay S, Haury M, Demengeot J. Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide. J Exp Med 2003;197: 403-411.
188. Crellin NK, Garcia RV, Hadisfar O, Allan SE, Steiner T, Levings MK. Human CD4+ T cells express TLR5 and its ligand flagellin enhances the suppressive capacity and expression of FOXP3 in CD4+CD25+ T regulatory cells. J Immunol 2005;175:8051-8059.
189. Re F, Strominger JL. IL-10 released by concomitant TLR2 stimulation blocks the induction of a subset of Th1 cytokines that are specifically induced by TLR4 or TLR3 in human dendritic cells. J Immunol 2004;173:7548-7555.
190. Rogers NC, et al. Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity 2005;22:507-517.
191. Higgins SC, et al. Toll-like receptor 4-mediated innate IL-10 activates antigen-specific regulatory T cells and confers resistance to Bordetella pertussis by inhibiting inflammatory pathology. J Immunol 2003;171:3119-3127.
192. Fischer A. Human primary immunodeficiency diseases: a perspective. Nat Immunol 2004;5:23-30.
193. Trofe J, et al. Posttransplant malignancy. Prog Transplant 2004;14:193-200.
194. Hoshida Y, Aozasa K. Malignancies in organ transplant recipients. Pathol Int 2004;54:649-658.
195. Algarra I, Garcia-Lora A, Cabrera T, Ruiz-Cabello F, Garrido F. The selection of tumor variants with altered expression of classical and nonclassical MHC class I molecules: implications for tumor immune escape. Cancer Immunol Immunother 2004;53:904-910.
196. Garrido F, Algarra I. MHC antigens and tumor escape from immune surveillance. Adv Cancer Res 2001;83:117-158.
197. Khong HT, Wang QJ, Rosenberg SA. Identification of multiple antigens recognized by tumor-infiltrating lymphocytes from a single patient: tumor escape by antigen loss and loss of MHC expression. J Immunother 2004;27:184-190.
198. Sjoberg J, et al. Interleukin-10 mRNA expression in B-cell chronic lymphocytic leukaemia inversely correlates with progression of disease. Br J Haematol 1996;92:393-400.
199. Rouleau M, et al. IL-10 transgenic mice present a defect in T cell development reminiscent of SCID patients. J Immunol 1999;163:1420-1427.
200. Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 2005;6:345-352.
201. Nomura T, Sakaguchi S. Naturally arising CD25+CD4+ regulatory T cells in tumor immunity. Curr Top Microbiol Immunol 2005;293:287-302.
202. Shevach EM. Fatal attraction: tumors beckon regulatory T cells. Nat Med 2004;10:900-901.
203. Yu P, et al. Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. J Exp Med 2005;201:779-791.
204. Ghiringhelli F, et al. CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur J Immunol 2004;34:336-344.
205. Erdman SE, et al. CD4(+)CD25(+) regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice. Cancer Res 2003;63:6042-6050.
206. Erdman SE, et al. CD4+CD25+ regulatory lymphocytes induce regression of intestinal tumors in ApcMin/+ mice. Cancer Res 2005;65:3998-4004.
207. Curiel TJ, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004;10:942-949.
208. Liyanage UK, et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol 2002;169:2756-2761.
209. Wang HY, et al. Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity 2004;20:107-118.
210. Ahmadzadeh M, Rosenberg SA. IL-2 Administration Increases CD4+CD25hiFoxp3+ Regulatory T Cells in Cancer Patients. Blood 2006;107:2409-2414.
211. Beyer M, et al. Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine. Blood 2005;106:2018-2025.
212. Seo S, Buckler J, Erikson J. Novel roles for Lyn in B cell migration and lipopolysaccharide responsiveness revealed using anti-double-stranded DNA Ig transgenic mice. J Immunol 2001;166:3710-3716.
213. Segal BM, Glass DD, Shevach EM. Cutting Edge: IL-10-producing CD4+ T cells mediate tumor rejection. J Immunol 2002;168:1-4.
214. Anderson MS, Venanzi ES, Chen Z, Berzins SP, Benoist C, Mathis D. The cellular mechanism of Aire control of T cell tolerance. Immunity 2005;23:227-239.
215. Eisenbarth GS, Gottlieb PA. Autoimmune polyendocrine syndromes. N Engl J Med 2004;350:2068-2079.
216. Kriegel MA, Lohmann T, Gabler C, Blank N, Kalden JR, Lorenz HM. Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II. J Exp Med 2004;199:1285-1291.
217. Wildin RS, Smyk-Pearson S, Filipovich AH. Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Genet 2002;39:537-545.
218. Bacchetta R, et al. Defective regulatory and effector T cell functions in patients with FoxP3 mutations. J Clin Invest 2006;116:1713-1722.
219. Schubert LA, Jeffery E, Zhang Y, Ramsdell F, Ziegler SF. Scurfin (FOXP3) acts as a repressor of transcription and regulates T cell activation. J Biol Chem 2001;276:37672-37679.
220. Bettelli E, Dastrange M, Oukka M. 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 USA 2005;102:5138-5143.
221. Storb R. Allogeneic hematopoietic stem cell transplantation-yesterday, today, and tomorrow. Exp Hematol 2003;31:1-10.
222. Riddell SR, Berger C, Murata M, Randolph S, Warren EH. The graft versus leukemia response after allogeneic hematopoietic stem cell transplantation. Blood Rev 2003;17:153-162.
223. Kolb HJ, Schmid C, Barrett AJ, Schendel DJ. Graft-versus-leukemia reactions in allogeneic chimeras. Blood 2004;103:767-776.
224. Riddell SR. Finding a place for tumor-specific T cells in targeted cancer therapy. J Exp Med 2004;200:1533-1537.
225. Ciceri F, Bonini C, Gallo-Stampino C, Bordignon C. Modulation of GvHD by suicide-gene transduced donor T lymphocytes: clinical applications in mismatched transplantation. Cytotherapy 2005;7:144-149.
226. Bluestone JA. Regulatory T-cell therapy: is it ready for the clinic? Nat Rev Immunol 2005;5:343-349.
227. Edinger M, et al. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med 2003;9:1144-1150.
228. Wysocki CA, et al. Critical role for CCR5 in the function of donor CD4+CD25+ regulatory T cells during acute graft-versus-host disease. Blood 2005;106:3300-3307.
229. Wang XN, et al. Interleukin-10 modulation of alloreactivity and graft-versus-host reactions. Transplantation 2002;74:772-778.
230. Bacchetta R, Gregori S, Roncarolo MG. CD4+ regulatory T cells: mechanisms of induction and effector function. Autoimmun Rev 2005;4:491-496.
231. Spits H, Touraine JL, Yssel H, de Vries JE, Roncarolo MG. Presence of host-reactive and MHC-restricted T cells in a transplanted severe combined immunodeficient (SCID) patient suggest positive selection and absence of clonal deletion. Immunol Rev 1990;116:101-116.
232. Roncarolo MG, Bacchetta R, Bordignon C, Narula S, Levings MK. Type 1 T regulatory cells. Immunol Rev 2001;182:68-79.
233. Masteller EL, et al. Peptide-MHC class II dimers as therapeutics to modulate antigen-specific T cell responses in autoimmune diabetes. J Immunol 2003;171:5587-5595.
234. Casares S, Hurtado A, McEvoy RC, Sarukhan A, von Boehmer H, Brumeanu TD. Down-regulation of diabetogenic CD4+ T cells by a soluble dimeric peptide-MHC class II chimera. Nat Immunol 2002;3:383-391.
235. Chen C, Lee WH, Yun P, Snow P, Liu CP. Induction of autoantigen-specific Th2 and Tr1 regulatory T cells and modulation of autoimmune diabetes. J Immunol 2003;171:733-744.
236. You S, Chen C, Lee WH, Brusko T, Atkinson M, Liu CP. Presence of diabetes-inhibiting, glutamic acid decarboxylase-specific, IL-10-dependent, regulatory T cells in naive nonobese diabetic mice. J Immunol 2004;173:6777-6785.
237. Wildbaum G, Netzer N, Karin N. Tr1 cell-dependent active tolerance blunts the pathogenic effects of determinant spreading. J Clin Invest 2002;110:701-710.
238. Frenkel D, et al. Nasal vaccination with myelin oligodendrocyte glycoprotein reduces stroke size by inducing IL-10-producing CD4+ T cells. J Immunol 2003;171:6549-6555.
239. Zuany-Amorim C, et al. Long-term protective and antigen-specific effect of heat-killed Mycobacterium vaccae in a murine model of allergic pulmonary inflammation. J Immunol 2002;169:1492-1499.
240. Stock P, Akbari O, Berry G, Freeman GJ, Dekruyff RH, Umetsu DT. Induction of T helper type 1-like regulatory cells that express Foxp3 and protect against airway hyper-reactivity. Nat Immunol 2004;5:1149-1156.
241. Doetze A, et al. Antigen-specific cellular hyporesponsiveness in a chronic human helminth infection is mediated by T(h)3/T(r)1-type cy tokines IL-10 and transforming growth factor-beta but not by a T(h)1 to T(h)2 shift. Int Immunol 2000;12:623-630.
242. Plebanski M, et al. Interleukin 10-mediated immunosuppression by a variant CD4 T cell epitope of Plasmodium falciparum. Immunity 1999;10:651-660.
243. Lecart S, et al. Phenotypic characterization of human CD4+ regulatory T cells obtained from cutaneous dinitrochlorobenzene-induced delayed type hypersensitivity reactions. J Invest Dermatol 2001;117:318-325.
244. Jutel M, et al. IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol 2003;33:1205-1214.
245. Francis JN, Till SJ, Durham SR. Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy. J Allergy Clin Immunol 2003;111:1255-1261.