The B10 Idd9.3 locus mediates accumulation of functionally superior CD137+ regulatory T cells in the nonobese diabetic type 1 diabetes model

Journal of Immunology

Volumn 189, Issue 10, 2012, Pages 5001-5015

  Kachapati, Kritika ^a   Adams, David E ^a   Wu, Yuehong ^a   Steward, Charles A ^b   Rainbow, Daniel B ^c   Wicker, Linda S ^c   Mittler, Robert S ^d,e   Ridgway, William M ^a  

^a UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

^b WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^c UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^d EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e EMORY UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD137 ANTIGEN;

AGE; AMINO ACID SEQUENCE; ANIMAL CELL; ANIMAL TISSUE; ANTIGEN EXPRESSION; ANTIGEN FUNCTION; ARTICLE; CD4+ CD25+ T LYMPHOCYTE; CONTROLLED STUDY; DISEASE PREDISPOSITION; DOWN REGULATION; ENZYME LINKED IMMUNOSORBENT ASSAY; GENE LOCUS; IN VITRO STUDY; IN VIVO STUDY; INSULIN DEPENDENT DIABETES MELLITUS; INTRACELLULAR SIGNALING; LYMPHOCYTE COUNT; LYMPHOCYTE PROLIFERATION; MOLECULAR PATHOLOGY; MOUSE; NONHUMAN; NONOBESE DIABETIC MOUSE; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE;

AGING; ANIMALS; ANTIGENS, CD137; BONE MARROW TRANSPLANTATION; DIABETES MELLITUS, EXPERIMENTAL; DIABETES MELLITUS, TYPE 1; GENETIC LOCI; GENETIC PREDISPOSITION TO DISEASE; MICE; MICE, INBRED NOD; MICE, TRANSGENIC; PROTEIN ISOFORMS; T-LYMPHOCYTES, REGULATORY; TRANSPLANTATION CHIMERA; TRANSPLANTATION, HOMOLOGOUS;

EID: 84868570652     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1101013     Document Type: Article

References (59)

1. Bluestone, J. A., K. Herold, and G. Eisenbarth. 2010. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature 464: 1293-1300.
2. Cannons, J. L., G. Chamberlain, J. Howson, L. J. Smink, J. A. Todd, L. B. Peterson, L. S. Wicker, and T. H. Watts. 2005. Genetic and functional association of the immune signaling molecule 4-1BB (CD137/TNFRSF9) with type 1 diabetes. J. Autoimmun. 25: 13-20.
3. Lyons, P. A., W. W. Hancock, P. Denny, C. J. Lord, N. J. Hill, N. Armitage, T. Siegmund, J. A. Todd, M. S. Phillips, J. F. Hess, et al. 2000. The NOD Idd9 genetic interval influences the pathogenicity of insulitis and contains molecular variants of Cd30, Tnfr2, and Cd137. Immunity 13: 107-115.
4. Watts, T. H. 2005. TNF/TNFR family members in costimulation of T cell responses. Annu. Rev. Immunol. 23: 23-68.
5. Irie, J., Y. Wu, K. Kachapati, R. S. Mittler, and W. M. Ridgway. 2007. Modulating protective and pathogenic CD4+ subsets via CD137 in type 1 diabetes. Diabetes 56: 186-196.
6. Zheng, G., B. Wang, and A. Chen. 2004. The 4-1BB costimulation augments the proliferation of CD4+CD25+ regulatory T cells. J. Immunol. 173: 2428-2434.
7. Gavin, M. A., S. R. Clarke, E. Negrou, A. Gallegos, and A. Rudensky. 2002. Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivo. Nat. Immunol. 3: 33-41.
8. McHugh, R. S., M. J. Whitters, C. A. Piccirillo, D. A. Young, E. M. Shevach, M. Collins, and M. C. Byrne. 2002. CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 16: 311-323.
9. Choi, B. K., J. S. Bae, E. M. Choi, W. J. Kang, S. Sakaguchi, D. S. Vinay, and B. S. Kwon. 2004. 4-1BB-dependent inhibition of immunosuppression by activated CD4+CD25+ T cells. J. Leukoc. Biol. 75: 785-791.
10. Marson, A., K. Kretschmer, G. M. Frampton, E. S. Jacobsen, J. K. Polansky, K. D. MacIsaac, S. S. Levine, E. Fraenkel, H. von Boehmer, and R. A. Young. 2007. Foxp3 occupancy and regulation of key target genes during T-cell stimulation. Nature 445: 931-935.
11. Chen, Z., A. E. Herman, M. Matos, D. Mathis, and C. Benoist. 2005. Where CD4+ CD25+ T reg cells impinge on autoimmune diabetes. J. Exp. Med. 202: 1387-1397.
12. Hamilton-Williams, E. E., S. B. Wong, X. Martinez, D. B. Rainbow, K. M. Hunter, L. S. Wicker, and L. A. Sherman. 2010. Idd9.2 and Idd9.3 protective alleles function in CD4+ T-cells and nonlymphoid cells to prevent expansion of pathogenic islet-specific CD8+ T-cells. Diabetes 59: 1478-1486.
13. Elpek, K. G., E. S. Yolcu, D. D. Franke, C. Lacelle, R. H. Schabowsky, and H. Shirwan. 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.
14. Asseman, C., S. Mauze, M. W. Leach, R. L. Coffman, and F. Powrie. 1999. An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J. Exp. Med. 190: 995-1004.
15. -/-mice: in vivo suppression by CD4+CD25+ regulatory T cells independent of autocrine TGF-beta1. Blood 103: 4594-4601.
16. Garín, M. I., C. C. Chu, D. Golshayan, E. Cernuda-Morollón, R. Wait, and R. I. Lechler. 2007. Galectin-1: a key effector of regulation mediated by CD4 +CD25+ T cells. Blood 109: 2058-2065.
17. Collison, L. W., C. J. Workman, T. T. Kuo, K. Boyd, Y. Wang, K. M. Vignali, R. Cross, D. Sehy, R. S. Blumberg, and D. A. Vignali. 2007. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450: 566-569.
18. Baratelli, F., Y. Lin, L. Zhu, S. C. Yang, N. Heuzé-Vourc'h, G. Zeng, K. Reckamp, M. Dohadwala, S. Sharma, and S. M. Dubinett. 2005. Prosta-glandin E2 induces FOXP3 gene expression and T regulatory cell function in human CD4+ T cells. J. Immunol. 175: 1483-1490.
19. Chaturvedi, V., L. W. Collison, C. S. Guy, C. J. Workman, and D. A. Vignali. 2011. Cutting edge: Human regulatory T cells require IL-35 to mediate suppression and infectious tolerance. J. Immunol. 186: 6661-6666.
20. Chauhan, S. K., D. R. Saban, H. K. Lee, and R. Dana. 2009. Levels of Foxp3 in regulatory T cells reflect their functional status in transplantation. J. Immunol. 182: 148-153.
21. Chen, M. L., B. S. Yan, Y. Bando, V. K. Kuchroo, and H. L. Weiner. 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.
22. Collison, L. W., M. R. Pillai, V. Chaturvedi, and D. A. Vignali. 2009. Regulatory T cell suppression is potentiated by target T cells in a cell contact, IL-35-and IL-10-dependent manner. J. Immunol. 182: 6121-6128.
23. Fu, S., A. C. Yopp, X. Mao, D. Chen, N. Zhang, D. Chen, M. Mao, Y. Ding, and J. S. Bromberg. 2004. CD4+ CD25+ CD62+ T-regulatory cell subset has optimal suppressive and proliferative potential. Am. J. Transplant. 4: 65-78.
24. Jonuleit, H., E. Schmitt, H. Kakirman, M. Stassen, J. Knop, and A. H. Enk. 2002. Infectious tolerance: human CD25(+) regulatory T cells convey suppressor activity to conventional CD4(+) T helper cells. J. Exp. Med. 196: 255-260.
25. Kim, Y. G., C. K. Lee, S. S. Nah, S. H. Mun, B. Yoo, and H. B. Moon. 2007. Human CD4+CD25+ regulatory T cells inhibit the differentiation of osteoclasts from peripheral blood mononuclear cells. Biochem. Biophys. Res. Commun. 357: 1046-1052.
26. Lin, J., M. Li, Z. Wang, S. He, X. Ma, and D. Li. 2010. The role of CD4+CD25+ regulatory T cells in macrophage-derived foam-cell formation. J. Lipid Res. 51: 1208-1217.
27. Strauss, L., C. Bergmann, M. J. Szczepanski, S. Lang, J. M. Kirkwood, and T. L. Whiteside. 2008. Expression of ICOS on human melanoma-infiltrating CD4+CD25highFoxp3+ T regulatory cells: implications and impact on tumor-mediated immune suppression. J. Immunol. 180: 2967-2980.
28. Sun, L., S. Yi, and P. J. O'Connell. 2010. Foxp3 regulates human natural CD4+ CD25+ regulatory T-cell-mediated suppression of xenogeneic response. Xeno-transplantation 17: 121-130.
29. Szczepanski, M. J., M. Szajnik, M. Czystowska, M. Mandapathil, L. Strauss, A. Welsh, K. A. Foon, T. L. Whiteside, and M. Boyiadzis. 2009. Increased frequency and suppression by regulatory T cells in patients with acute mye-logenous leukemia. Clin. Cancer Res. 15: 3325-3332.
30. Setareh, M., H. Schwarz, and M. Lotz. 1995. A mRNA variant encoding a soluble form of 4-1BB, a member of the murine NGF/TNF receptor family. Gene 164: 311-315.
31. Jung, H. W., S. W. Choi, J. I. Choi, and B. S. Kwon. 2004. Serum concentrations of soluble 4-1BB and 4-1BB ligand correlated with the disease severity in rheumatoid arthritis. Exp. Mol. Med. 36: 13-22.
32. Shao, Z., F. Sun, D. R. Koh, and H. Schwarz. 2008. Characterisation of soluble murine CD137 and its association with systemic lupus. Mol. Immunol. 45: 3990-3999.
33. Michel, J., and H. Schwarz. 2000. Expression of soluble CD137 correlates with activation-induced cell death of lymphocytes. Cytokine 12: 742-746.
34. Hamilton-Williams, E. E., X. Martinez, J. Clark, S. Howlett, K. M. Hunter, D. B. Rainbow, L. Wen, M. J. Shlomchik, J. D. Katz, G. F. Beilhack, et al. 2009. Expression of diabetes-associated genes by dendritic cells and CD4 T cells drives the loss of tolerance in nonobese diabetic mice. J. Immunol. 183: 1533-1541.
35. Bettelli, E., Y. Carrier, W. Gao, T. Korn, T. B. Strom, M. Oukka, H. L. Weiner, and V. K. Kuchroo. 2006. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441: 235-238.
36. Foell, J., M. McCausland, J. Burch, N. Corriazzi, X. J. Yan, C. Suwyn, S. P. O'Neil, M. K. Hoffmann, and R. S. Mittler. 2003. CD137-mediated T cell co-stimulation terminates existing autoimmune disease in SLE-prone NZB/NZW F1 mice. Ann. N. Y. Acad. Sci. 987: 230-235.
37. Steward, C. A., S. Humphray, B. Plumb, M. C. Jones, M. A. Quail, S. Rice, T. Cox, R. Davies, J. Bonfield, T. M. Keane, et al. 2010. Genome-wide end-sequenced BAC resources for the NOD/MrkTac() and NOD/ShiLtJ() mouse genomes. Genomics 95: 105-110.
38. Ning, Z., A. J. Cox, and J. C. Mullikin. 2001. SSAHA: a fast search method for large DNA databases. Genome Res. 11: 1725-1729.
39. Hulbert, E. M., L. J. Smink, E. C. Adlem, J. E. Allen, D. B. Burdick, O. S. Burren, V. M. Cassen, C. C. Cavnor, G. E. Dolman, D. Flamez, et al. 2007. T1DBase: integration and presentation of complex data for type 1 diabetes research. Nucleic Acids Res. 35(Database issue): D742-D746.
40. Smink, L. J., E. M. Helton, B. C. Healy, C. C. Cavnor, A. C. Lam, D. Flamez, O. S. Burren, Y. Wang, G. E. Dolman, D. B. Burdick, et al. 2005. T1DBase, a community web-based resource for type 1 diabetes research. Nucleic Acids Res. 33(Database issue): D544-D549.
41. Stein, L. D., C. Mungall, S. Shu, M. Caudy, M. Mangone, A. Day, E. Nickerson, J. E. Stajich, T. W. Harris, A. Arva, and S. Lewis. 2002. The generic genome browser: a building block for a model organism system database. Genome Res. 12: 1599-1610.
42. Lee, H. W., S. J. Park, B. K. Choi, H. H. Kim, K. O. Nam, and B. S. Kwon. 2002. 4-1BB promotes the survival of CD8+ T lymphocytes by increasing expression of Bcl-xL and Bfl-1. J. Immunol. 169: 4882-4888.
43. Bertram, E. M., P. Lau, and T. H. Watts. 2002. Temporal segregation of 4-1BB versus CD28-mediated costimulation: 4-1BB ligand influences T cell numbers late in the primary response and regulates the size of the T cell memory response following influenza infection. J. Immunol. 168: 3777-3785.
44. Pop, S. M., C. P. Wong, D. A. Culton, S. H. Clarke, and R. Tisch. 2005. Single cell analysis shows decreasing FoxP3 and TGFbeta1 coexpressing CD4+CD25+ regulatory T cells during autoimmune diabetes. J. Exp. Med. 201: 1333-1346.
45. Kim, J., S. P. Choi, S. La, J. S. Seo, K. K. Kim, S. H. Nam, and B. Kwon. 2003. Constitutive expression of 4-1BB on T cells enhances CD4+ T cell responses. Exp. Mol. Med. 35: 509-517.
46. Mellanby, R. J., D. Thomas, J. M. Phillips, and A. Cooke. 2007. Diabetes in non-obese diabetic mice is not associated with quantitative changes in CD4+ CD25+ Foxp3+ regulatory T cells. Immunology 121: 15-28.
47. Cannons, J. L., P. Lau, B. Ghumman, M. A. DeBenedette, H. Yagita, K. Okumura, and T. H. Watts. 2001. 4-1BB ligand induces cell division, sustains survival, and enhances effector function of CD4 and CD8 T cells with similar efficacy. J. Immunol. 167: 1313-1324.
48. Hurtado, J. C., Y. J. Kim, and B. S. Kwon. 1997. Signals through 4-1BB are costimulatory to previously activated splenic T cells and inhibit activation-induced cell death. J. Immunol. 158: 2600-2609.
49. Gregg, R. K., R. Jain, S. J. Schoenleber, R. Divekar, J. J. Bell, H. H. Lee, P. Yu, and H. Zaghouani. 2004. A sudden decline in active membrane-bound TGF-beta impairs both T regulatory cell function and protection against autoimmune diabetes. J. Immunol. 173: 7308-7316.
50. Thomas, D. C., R. J. Mellanby, J. M. Phillips, and A. Cooke. 2007. An early age-related increase in the frequency of CD4+ Foxp3+ cells in BDC2.5NOD mice. Immunology 121: 565-576.
51. Nolte-'t Hoen, E. N., J. P. Wagenaar-Hilbers, E. P. Boot, C. H. Lin, G. J. Arkesteijn, W. van Eden, L. S. Taams, and M. H. Wauben. 2004. Identification of a CD4+CD25+ T cell subset committed in vivo to suppress antigen-specific T cell responses without additional stimulation. Eur. J. Immunol. 34: 3016-3027.
52. Lehmann, J., J. Huehn, M. de la Rosa, F. Maszyna, U. Kretschmer, V. Krenn, M. Brunner, A. Scheffold, and A. Hamann. 2002. Expression of the integrin alpha Ebeta 7 identifies unique subsets of CD25+ as well as CD25-regulatory T cells. Proc. Natl. Acad. Sci. USA 99: 13031-13036.
53. Szanya, V., J. Ermann, C. Taylor, C. Holness, and C. G. Fathman. 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.
54. Hoffmann, P., R. Eder, T. J. Boeld, K. Doser, B. Piseshka, R. Andreesen, and M. Edinger. 2006. Only the CD45RA+ subpopulation of CD4+CD25high T cells gives rise to homogeneous regulatory T-cell lines upon in vitro expansion. Blood 108: 4260-4267.
55. Kohm, A. P., and S. D. Miller. 2003. Role of ICAM-1 and P-selectin expression in the development and effector function of CD4+CD25+regulatory T cells. J. Autoimmun. 21: 261-271.
56. Liu, G. Z., A. C. Gomes, L. B. Fang, X. G. Gao, and P. Hjelmstrom. 2008. Decreased 4-1BB expression on CD4+CD25 high regulatory T cells in peripheral blood of patients with multiple sclerosis. Clin. Exp. Immunol. 154: 22-29.
57. Liu, G. Z., A. C. Gomes, P. Putheti, V. Karrenbauer, K. Kostulas, R. Press, J. Hillert, P. Hjelmström, and X. G. Gao. 2006. Increased soluble 4-1BB ligand (4-1BBL) levels in peripheral blood of patients with multiple sclerosis. Scand. J. Immunol. 64: 412-419.
58. Sharief, M. K. 2002. Heightened intrathecal release of soluble CD137 in patients with multiple sclerosis. Eur. J. Neurol. 9: 49-54.
59. Hurtado, J. C., S. H. Kim, K. E. Pollok, Z. H. Lee, and B. S. Kwon. 1995. Potential role of 4-1BB in T cell activation. Comparison with the costimulatory molecule CD28. J. Immunol. 155: 3360-3367.