Regulatory T cells enter the pancreas during suppression of type 1 diabetes and inhibit effector T cells and macrophages in a TGF-β-dependent manner

European Journal of Immunology

Volumn 39, Issue 5, 2009, Pages 1313-1322

  Tonkin, Daniel R ^a   Haskins, Kathryn ^a  

^a UNIVERSITY OF COLORADO   (United States)

Author keywords

Autoimmunity; Diabetes; Rodent; Tolerance; Treg

Indexed keywords

CD11 ANTIGEN; CHEMOKINE; CYTOKINE; INTERLEUKIN 10; INTERLEUKIN 1BETA; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MACROPHAGE INFLAMMATORY PROTEIN 1BETA; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR; TUMOR NECROSIS FACTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CD4 LYMPHOCYTE COUNT; CD4+ T LYMPHOCYTE; CELLULAR IMMUNITY; CONTROLLED STUDY; CYTOKINE PRODUCTION; EFFECTOR CELL; GENETIC TRANSFECTION; IN VITRO STUDY; INFLAMMATION; INSULIN DEPENDENT DIABETES MELLITUS; LYMPH NODE; LYMPHOCYTE TRANSFER; LYMPHOCYTIC INFILTRATION; MACROPHAGE; MOUSE; NONHUMAN; PANCREAS; PRIORITY JOURNAL; PROTEIN SYNTHESIS INHIBITION; REGULATORY T LYMPHOCYTE; SPLEEN CELL; T LYMPHOCYTE ACTIVATION; TH1 CELL; TRANSGENIC MOUSE; ADOPTIVE TRANSFER; ANIMAL; BLOOD; DRUG ANTAGONISM; DRUG EFFECT; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; GERMFREE ANIMAL; IMMUNOLOGY; MALE; MOUSE MUTANT; NONOBESE DIABETIC MOUSE;

ADOPTIVE TRANSFER; ANIMALS; CYTOKINES; DIABETES MELLITUS, TYPE 1; ENZYME-LINKED IMMUNOSORBENT ASSAY; FEMALE; MACROPHAGES; MALE; MICE; MICE, INBRED NOD; MICE, SCID; MICE, TRANSGENIC; PANCREAS; RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; SPECIFIC PATHOGEN-FREE ORGANISMS; T-LYMPHOCYTES, REGULATORY; TH1 CELLS; TRANSFORMING GROWTH FACTOR BETA;

EID: 67650003971     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.200838916     Document Type: Article

References (45)

1. Wu, A. J., Hua, H., Munson, S. H. and McDevitt, H. O., Tumor necrosis factor-alpha regulation of CD4+CD25+ T cell levels in NOD mice. Proc. Natl. Acad. Sci. USA 2002, 12287-12292.
2. Tang, Q., Henriksen, K. J., Bi, M., Finger, E. B., Szot, G., Ye, J., Masteller, E. L. et al., In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J. Exp. Med. 2004. 199: 1455-1465.
3. You, S., Belghith, M., Cobbold, S., Alyanakian, M. A., Gouarin, C., Barriot, S., Garcia, C. et al., Autoimmune diabetes onset results from qualitative rather than quantitative age-dependent changes in pathogenic T-cells. Diabetes 2005. 54: 1415-1422.
4. Tarbell, K. V., Petit, L., Zuo, X., Toy, P., Luo, X., Mqadmi, A., Yang, H. et al., Dendritic cell-expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice. J. Exp. Med. 2007. 204: 191-201.
5. Weber, S. E., Harbertson, J., Godebu, E., Mros, G. A., Padrick, R. C., Carson, B. D., Ziegler, S. F. and Bradley, L. M., Adaptive islet-specific regulatory CD4 T cells control autoimmune diabetes and mediate the disappearance of pathogenic Th1 cells in vivo. J. Immunol. 2006. 176: 4730-4739.
6. Tonkin, D. R., He, J., Barbour, G. and Haskins, K., Regulatory T cells prevent transfer of type 1 diabetes in NOD mice only when their antigen is present in vivo. J. Immunol. 2008. 181: 4516-4522.
7. Shevach, E. M., McHugh, R. S., Piccirillo, C. A. and Thornton, A. M., Control of T-cell activation by CD4+ CD25+ suppressor T cells. Immunol. Rev. 2001. 182: 58-67.
8. Pandiyan, P., Zheng, L., Ishihara, S., Reed, J. and Lenardo, M. J., CD4+ CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat. Immunol. 2007. 8: 1353-1362.
9. Grossman, W. J., Verbsky, J. W., Barchet, W., Colonna, M., Atkinson, J. P. and Ley, T. J., Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity 2004. 21: 589-601.
10. Gondek, D. C., Lu, L. F., Quezada, S. A., Sakaguchi, S. and Noelle, R. J., Cutting edge: Contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. J. Immunol. 2005. 174: 1783-1786.
11. Salomon, B., Lenschow, D. J., Rhee, L., Ashourian, N., Singh, B., Sharpe, A. and Bluestone, J. A., B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 2000. 12: 431-440.
12. Zheng, S. G., Wang, J. H., Gray, J. D., Soucier, H. and Horwitz, D. A., Natural and induced CD4+CD25+ cells educate CD4+CD25- cells to develop suppressive activity: The role of IL-2, TGF-beta, and IL-10. J. Immunol. 2004. 172: 5213-5221.
13. Huang, X., Zhu, J. and Yang, Y., Protection against autoimmunity in nonlymphopenic hosts by CD4+ CD25+ regulatory T cells is antigen-specific and requires IL-10 and TGF-beta. J. Immunol. 2005. 175: 4283-4291.
14. Lu, L. F., Lind, E. F., Gondek, D. C., Bennett, K. A., Gleeson, M. W., Pino-Lagos, K., Scott, Z. A. et al., Mast cells are essential intermediaries in regulatory T-cell tolerance. Nature 2006. 442: 997-1002.
15. Collison, L. W., Workman, C. J., Kuo, T. T., Boyd, K., Wang, Y., Vignali, K. M., Cross, R. et al., The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 2007. 450: 566-569.
16. Nakamura, K., Kitani, A. and Strober, W. i., Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta. J. Exp. Med. 2001. 194: 629-644.
17. Green, E. A., Gorelik, L., McGregor, C. M., Tran, E. H. and Flavell, R. A., 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. USA 2003. 100: 10878-10883.
18. Piccirillo, C. A., Letterio, J. J., Thornton, A. M., McHugh, R. S., Mamura, M., Mizuhara, H. and Shevach, E. M., 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.
19. Fantini, M. C., Becker, C., Monteleone, G., Pallone, F., Galle, P. R. and Neurath, M. F., Cutting edge: TGF-beta induces a regulatory phenotype in CD4+CD25- T cells through Foxp3 induction and down-regulation of Smad7. J. Immunol. 2004. 172: 5149-5153.
20. You, S., Thieblemont, N., Alyanakian, M. A., Bach, J. F. and Chatenoud, L., Transforming growth factor-beta and T-cell-mediated immunoregulation in the control of autoimmune diabetes. Immunol. Rev. 2006. 212: 185-202.
21. Schramm, C., Huber, S., Protschka, M., Czochra, P., Burg, J., Schmitt, E., Lohse, A.W. et al., TGFbeta regulates the CD4+CD25+ T-cell pool and the expression of Foxp3 in vivo. Int. Immunol. 2004. 16: 1241-1249.
22. Belghith, M., Bluestone, J. A., Barriot, S., Megret, J., Bach, J. F. and 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.
23. Chen, M. L., Pittet, M. J., Gorelik, L., Flavell, R. A., Weissleder, R., von Boehmer, H. and Khazaie, K., Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo. Proc. Natl. Acad. Sci. USA 2005. 102: 419-424.
24. Fahlen, L., Read, S., Gorelik, L., Hurst, S. D., Coffman, R. L., Flavell, R. A. and Powrie, F., T cells that cannot respond to TGF-beta escape control by CD4(+)CD25(+) regulatory T cells. J. Exp. Med. 2005. 201: 737-746.
25. Du, W., Wong, F. S., Li, M. O., Peng, J., Qi, H., Flavell, R. A., Sherwin, R. and Wen, L., TGF-beta signaling is required for the function of insulin-reactive T regulatory cells. J. Clin. Invest. 2006. 116: 1360-1370.
26. Kullberg, M. C., Hay, V., Cheever, A. W., Mamura, M., Sher, A., Letterio, J. J., Shevach, E. M. and Piccirillo, C. A., TGF-beta1 production by CD4+ CD25+ regulatory T cells is not essential for suppression of intestinal inflammation. Eur. J. Immunol. 2005. 35: 2886-2895.
27. Tang, Q., Adams, J. Y., Tooley, A. J., Bi, M., Fife, B. T., Serra, P., Santamaria, P. et al., Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice. Nat. Immunol. 2006. 7: 83-92.
28. Cantor, J. and Haskins, K., Effector function of diabetogenic CD4 Th1 T cell clones: A central role for TNF-alpha. J. Immunol. 2005. 175: 7738-7745.
29. Kurrer, M. O., Pakala, S. V., Hanson, H. L. and Katz, J. D., Beta cell apoptosis in T cell-mediated autoimmune diabetes. Proc. Natl. Acad. Sci. USA 1997. 94: 213-218.
30. Dobbs, C. and Haskins, K., Comparison of a T cell clone and of T cells from a TCR transgenic mouse: TCR transgenic T cells specific for self-antigen are atypical. J. Immunol. 2001. 166: 2495-2504.
31. Kanagawa, O., Militech, A. and Vaupel, B. A., Regulation of diabetes development by regulatory T cells in pancreatic islet antigen-specific TCR transgenic nonobese diabetic mice. J. Immunol. 2002. 168: 6159-6164.
32. Chen, W., Jin, W., Hardegen, N., Lei, K. J., Li, L., Marinos, N., McGrady, G. and Wahl, S. M., 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. 2003. 198: 1875-1886.
33. Mekala, D. J., Alli, R. S. and Geiger, T. L., IL-10-dependent infectious tolerance after the treatment of experimental allergic encephalomyelitis with redirected CD4+CD25+ T lymphocytes. Proc. Natl. Acad. Sci. USA 2005. 102: 11817-11822.
34. Freire-de-Lima, C. G., Xiao, Y. Q., Gardai, S. J., Bratton, D. L., Schiemann, W. P. and Henson, P. M., Apoptotic cells, through transforming growth factor-beta, coordinately induce anti-inflammatory and suppress proinflammatory eicosanoid and NO synthesis in murine macrophages. J. Biol. Chem. 2006. 281: 38376-38384.
35. Yoon, J. W., Jun, H. S. and Santamaria, P., Cellular and molecular mechanisms for the initiation and progression of beta cell destruction resulting from the collaboration between macrophages and T cells. Autoimmunity 1998. 27: 109-122.
36. Cantor, J. and Haskins, K., Recruitment and activation of macrophages by pathogenic CD4 T cells in type 1 diabetes: Evidence for involvement of CCR8 and CCL1. J. Immunol. 2007. 179: 5760-5767.
37. Yang, X. D., Tisch, R., Singer, S.M., Cao, Z. A., Liblau, R. S., Schreiber, R. D. and McDevitt, H. O., Effect of tumor necrosis factor alpha on insulin-dependent diabetes mellitus in NOD mice. I. The early development of autoimmunity and the diabetogenic process. J. Exp. Med. 1994. 180: 995-1004.
38. Serreze, D. V., Chapman, H. D., Post, C. M., Johnson, E. A., Suarez-Pinzon, W. L. and Rabinovitch, A., Th1 to Th2 cytokine shifts in nonobese diabetic mice: Sometimes an outcome, rather than the cause, of diabetes resistance elicited by immunostimulation. J. Immunol. 2001. 166: 1352-1359.
39. Filippi, C. M., Juedes, A. E., Oldham, J. E., Ling, E., Togher, L., Peng, Y., Flavell, R. A. and von Herrath, M. G., Transforming growth factor-beta suppresses the activation of CD8+ T-cells when naive but promotes their survival and function once antigen experienced: A two-faced impact on autoimmunity. Diabetes 2008. 57: 2684-2692.
40. Marie, J. C., Liggitt, D. and Rudensky, A. Y., Cellular mechanisms of fatal early-onset autoimmunity in mice with the T cell-specific targeting of transforming growth factor-beta receptor. Immunity 2006. 25: 441-454.
41. Jonuleit, H., Schmitt, E., Kakirman, H., Stassen, M., Knop, J. and Enk, A. H., Infectious tolerance: Human CD25(+) regulatory T cells convey suppressor activity to conventional CD4(+) T helper cells. J. Exp. Med. 2002. 196: 255-260.
42. Andersson, J., Tran, D. Q., Pesu, M., Davidson, T. S., Ramsey, H., O'Shea, J. J. and Shevach, E. M., CD4+ FoxP3+ regulatory T cells confer infectious tolerance in a TGF-beta-dependent manner. J. Exp. Med. 2008. 205: 1975-1981.
43. Katz, J. D., Wang, B., Haskins, K., Benoist, C. and Mathis, D., Following a diabetogenic T cell from genesis through pathogenesis. Cell 1993. 74: 1089-1100.
44. Pauza, M. E., Dobbs, C. M., He, J., Patterson, T., Wagner, S., Anobile, B. S., Bradley, B. J. et al., T-cell receptor transgenic response to an endogenous polymorphic autoantigen determines susceptibility to diabetes. Diabetes 2004. 53: 978-988.
45. Mitchell, T. C., Hildeman, D., Kedl, R. M., Teague, T. K., Schaefer, B. C., White, J., Zhu, Y. et al., Immunological adjuvants promote activated T cell survival via induction of Bcl-3. Nat. Immunol. 2001. 2: 397-402.