The E3 ubiquitin ligase Cbl-b regulates expansion but not functional activity of self-reactive CD4 T cells

Journal of Immunology

Volumn 183, Issue 8, 2009, Pages 4975-4983

  St Rose, Marie Clare ^a   Qui, Harry Z ^a   Bandyopadhyay, Suman ^a   Mihalyo, Marianne A ^a   Hagymasi, Adam T ^a   Clark, Robert B ^a   Adler, Adam J ^a  

^a UNIVERSITY OF CONNECTICUT HEALTH CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN; PROTEIN CBL B; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ANTIGEN EXPRESSION; ANTIGEN PRESENTATION; ARTICLE; CD4+ T LYMPHOCYTE; CELL ACTIVITY; CELL EXPANSION; CLONAL ANERGY; CONTROLLED STUDY; IMMUNOREGULATION; IMMUNOSTIMULATION; IN VIVO STUDY; LYMPHOCYTE PROLIFERATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; REGULATORY MECHANISM; WILD TYPE;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ADOPTIVE TRANSFER; ANIMALS; ANTIGENS, CD28; CD4-POSITIVE T-LYMPHOCYTES; CELL CYCLE; CELL PROLIFERATION; MICE; MICE, KNOCKOUT; PROTO-ONCOGENE PROTEINS C-CBL;

EID: 77954127753     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.0901243     Document Type: Article

References (67)

1. Kappler, J., M. Roehm, and P. Marrack. 1987. T cell tolerance by clonal elimination in the thymus. Cell 49: 273-280.
2. + thymocytes. Nature 333: 742-746.
3. Surh, C. D., and J. Sprent. 1994. T-cell apoptosis detected in situ during positive and negative selection in the thymus. Nature 372: 100-103.
4. Derbinski, J., A. Schulte, B. Kyewski, and L. Klein. 2001. Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nat. Immunol. 2: 1032-1039.
5. Anderson, M. S., E. S. Venanzi, L. Klein, Z. Chen, S. P. Berzins, S. J. Turley, H. von Boehmer, R. Bronson, A. Dierich, C. Benoist, and D. Mathis. 2002. Projection of an immunological self shadow within the thymus by the aire protein. Science 298: 1395-1401.
6. Derbinski, J., S. Pinto, S. Rosch, K. Hexel, and B. Kyewski. 2008. Promiscuous gene expression patterns in single medullary thymic epithelial cells argue for a stochastic mechanism. Proc. Natl. Acad. Sci. USA 105: 657-662.
7. Bouneaud, C., P. Kourilsky, and P. Bousso. 2000. Impact of negative selection on the T cell repertoire reactive to a self-peptide: a large fraction of T cell clones escapes clonal deletion. Immunity 13: 829-840.
8. Von Budingen, H. C., N. Tanuma, P. Villoslada, J. C. Ouallet, S. L. Hauser, and C. P. Genain. 2001. Immune responses against the myelin/oligodendrocyte glycoprotein in experimental autoimmune demyelination. J. Clin. Immunol. 21: 155-170.
9. + T cells recognizing a single self-peptide expressed by APCs induce spontaneous autoimmune arthritis. J. Immunol. 180: 833-841.
10. Lo, D., L. C. Burkly, R. A. Flavell, R. D. Palmiter, and R. L. Brinster. 1989. Tolerance in transgenic mice expressing class II major histocompatibility complex on pancreatic acinar cells. J. Exp. Med. 170: 87-104.
11. Ohashi, P. S. 2002. T-cell signalling and autoimmunity: molecular mechanisms of disease. Nat. Rev. Immunol. 2: 427-438.
12. Redmond, W. L., and L. A. Sherman. 2005. Peripheral tolerance of CD8 T lymphocytes. Immunity 22: 275-284.
13. Ohashi, P. S., S. Oehen, K. Buerki, H. Pircher, C. T. Ohashi, B. Odermatt, B. Malissen, R. M. Zinkernagel, and H. Hengartner. 1991. Ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice. Cell 65: 305-317.
14. Oldstone, M. B., M. Nerenberg, P. Southern, J. Price, and H. Lewicki. 1991. Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response. Cell 65: 319-331.
15. Kurts, C., J. F. A. P. Miller, R. M. Subramaniam, F. R. Carbone, and W. R. Heath. 1998. Major histocompatibility complex class I-restricted cross-presentation is biased towards high dose antigens and those released during cellular destruction. J. Exp. Med. 188: 409-414.
16. Drake, C. G., A. D. Doody, M. A. Mihalyo, C. T. Huang, E. Kelleher, S. Ravi, E. L. Hipkiss, D. B. Flies, E. P. Kennedy, M. Long, et al. 2005. Androgen ablation mitigates tolerance to a prostate/prostate cancer-restricted antigen. Cancer Cell 7: 239-249.
17. Sakaguchi, S. 2000. Regulatory T cells: key controllers of immunologic selftolerance. Cell 101: 455-458.
18. + suppressor T cells. J. Exp. Med. 193: F41-F46.
19. Yamaguchi, T., K. Hirota, K. Nagahama, K. Ohkawa, T. Takahashi, T. Nomura, and S. Sakaguchi. 2007. Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity 27: 145-159.
20. + regulatory T cells induced by an agonist self-peptide. Nat. Immunol. 2: 301-306.
21. +CD4 T cells in vivo after induction of peripheral tolerance with intravenous or oral antigen. J. Immunol. 167: 188-195.
22. Apostolou, I., and H. von Boehmer. 2004. In vivo instruction of suppressor commitment in naive T cells. J. Exp. Med. 199: 1401-1408.
23. Nagata, S., and P. Golstein. 1995. The Fas death factor. Science 267: 1449-1456.
24. Krueger, A., S. C. Fas, S. Baumann, and P. H. Krammer. 2003. The role of CD95 in the regulation of peripheral T-cell apoptosis. Immunol. Rev. 193: 58-69.
25. Duke, R. C., and J. J. Cohen. 1986. IL-2 addiction: withdrawal of growth factor activates a suicide program in dependent T cells. Lymphokine Res. 5: 289-299.
26. Schwartz, R. H. 2003. T cell anergy. Annu. Rev. Immunol. 21: 305-334.
27. Wells, A. D. 2009. New insights into the molecular basis of T cell anergy: anergy factors, avoidance sensors, and epigenetic imprinting. J. Immunol. 182: 7331-7341.
28. Rocha, B., and H. von Boehmer. 1991. Peripheral selection of the T cell repertoire. Science 251: 1225-1228.
29. Webb, S., C. Morris, and J. Sprent. 1990. Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity. Cell 63: 1249-1256. (Pubitemid 120035073)
30. Redmond, W. L., B. C. Marincek, and L. A. Sherman. 2005. Distinct requirements for deletion versus anergy during CD8 T cell peripheral tolerance in vivo. J. Immunol. 174: 2046-2053.
31. Matzinger, P. 1994. Tolerance, danger, and the extended family. Annu. Rev. Immunol. 12: 991-1045.
32. Hawiger, D., K. Inaba, Y. Dorsett, M. Guo, K. Mahnke, M. Rivera, J. V. Ravetch, R. M. Steinman, and M. C. Nussenzweig. 2001. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J. Exp. Med. 194: 769-779.
33. Jenkins, M. K., A. Khoruts, E. Ingulli, D. L. Mueller, S. J. McSorley, R. L. Reinhardt, A. Itano, and K. A. Pape. 2001. In vivo activation of antigen-specific CD4 T cells. Annu. Rev. Immunol. 19: 23-45.
34. Janeway, C. A., Jr., and R. Medzhitov. 2002. Innate immune recognition. Annu. Rev. Immunol. 20: 197-216.
35. Ohnmacht, C., A. Pullner, S. B. King, I. Drexler, S. Meier, T. Brocker, and D. Voehringer. 2009. Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity. J. Exp. Med. 206: 549-559.
36. + T cells in vivo. J. Immunol. 163: 2561-2567.
37. Hagymasi, A. T., A. M. Slaiby, M. A. Mihalyo, H. Z. Qui, D. J. Zammit, L. Lefrancois, and A. J. Adler. 2007. Steady state dendritic cells present parenchymal self-antigen and contribute to, but are not essential for, tolerization of naive and Th1 effector CD4 cells. J. Immunol. 179: 1524-1531.
38. Mueller, D. L. 2004. E3 ubiquitin ligases as T cell anergy factors. Nat. Immunol. 5: 883-890.
39. Loeser, S., and J. M. Penninger. 2007. Regulation of peripheral T cell tolerance by the E3 ubiquitin ligase Cbl-b. Semin. Immunol. 19: 206-214.
40. Jeon, M. S., A. Atfield, K. Venuprasad, C. Krawczyk, R. Sarao, C. Elly, C. Yang, S. Arya, K. Bachmaier, L. Su, et al. 2004. Essential role of the E3 ubiquitin ligase Cbl-b in T cell anergy induction. Immunity 21: 167-177.
41. Fang, D., H. Y. Wang, N. Fang, Y. Altman, C. Elly, and Y. C. Liu. 2001. Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells. J. Biol. Chem. 276: 4872-4878.
42. Bachmaier, K., C. Krawczyk, I. Kozieradzki, Y. Y. Kong, T. Sasaki, A. Oliveira-dos-Santos, S. Mariathasan, D. Bouchard, A. Wakeham, A. Itie, et al. 2000. Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b. Nature 403: 211-216.
43. Chiang, Y. J., H. K. Kole, K. Brown, M. Naramura, S. Fukuhara, R. J. Hu, I. K. Jang, J. S. Gutkind, E. Shevach, and H. Gu. 2000. Cbl-b regulates the CD28 dependence of T-cell activation. Nature 403: 216-220.
44. -/- mice. J. Immunol. 173: 1059-1065.
45. Wohlfert, E. A., L. Gorelik, R. Mittler, R. A. Flavell, and R. B. Clark. 2006. Cutting edge: deficiency in the E3 ubiquitin ligase Cbl-b results in a multifunctional defect in T cell TGF-β sensitivity in vitro and in vivo. J. Immunol. 176: 1316-1320.
46. Yokoi, N., K. Komeda, H. Y. Wang, H. Yano, K. Kitada, Y. Saitoh, Y. Seino, K. Yasuda, T. Serikawa, and S. Seino. 2002. Cblb is a major susceptibility gene for rat type 1 diabetes mellitus. Nat. Genet. 31: 391-394.
47. Heissmeyer, V., F. Macian, S. H. Im, R. Varma, S. Feske, K. Venuprasad, H. Gu, Y. C. Liu, M. L. Dustin, and A. Rao. 2004. Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins. Nat. Immunol. 5: 255-265.
48. Safford, M., S. Collins, M. A. Lutz, A. Allen, C. T. Huang, J. Kowalski, A. Blackford, M. R. Horton, C. Drake, R. H. Schwartz, and J. D. Powell. 2005. Egr-2 and Egr-3 are negative regulators of T cell activation. Nat. Immunol. 6: 472-480.
49. + T cell tolerance induction versus priming is independent of the rate and number of cell divisions. J. Immunol. 164: 649-655.
50. Higgins, A. D., M. A. Mihalyo, P. W. McGary, and A. J. Adler. 2002. CD4 cell priming and tolerization are differentially programmed by APCs upon initial engagement. J. Immunol. 168: 5573-5581.
51. + single positive cells with a class II major histocompatibility complex-restricted receptor. J. Exp. Med. 180: 25-34.
52. + T cell tolerance to parenchymal self-antigens requires presentation by bone marrow-derived antigen presenting cells. J. Exp. Med. 187: 1555-1564.
53. Higgins, A. D., M. A. Mihalyo, and A. J. Adler. 2002. Effector CD4 cells are tolerized upon exposure to parenchymal self-antigen. J. Immunol. 169: 3622-3629.
54. Long, M., A. M. Slaiby, S. Wu, A. T. Hagymasi, M. A. Mihalyo, S. Bandyopadhyay, A. T. Vella, and A. J. Adler. 2007. Histone acetylation at the Ifng promoter in tolerized CD4 cells is associated with increased IFN-γ expression during subsequent immunization to the same antigen. J. Immunol. 179: 5669-5677.
55. Long, M., A. M. Slaiby, A. T. Hagymasi, M. A. Mihalyo, A. C. Lichtler, S. L. Reiner, and A. J. Adler. 2006. T-bet down-modulation in tolerized Th1 effector CD4 cells confers a TCR-distal signaling defect that selectively impairs IFN-γ expression. J. Immunol. 176: 1036-1045. (Pubitemid 43099704)
56. Long, M., A. D. Higgins, M. A. Mihalyo, and A. J. Adler. 2003. Effector CD4 cell tolerization is mediated through functional inactivation and involves preferential impairment of TNF-α and IFN-γ expression potentials. Cell. Immunol. 224: 114-121.
57. + T cell clonal expansion. J. Immunol. 181: 5331-5339.
58. Ramsdell, F., and B. J. Fowlkes. 1992. Maintenance of in vivo tolerance by persistence of antigen. Science 257: 1130-1134.
59. + T cells persist in vivo following induction of peripheral tolerance. J. Immunol. 160: 4719-4729.
60. + T cell proliferation and cytokine production but is not required for tuning T cell reactivity in adaptive tolerance. J. Immunol. 173: 7239-7248.
61. Bandyopadhyay, S., M. Long, H. Z. Qui, A. T. Hagymasi, A. M. Slaiby, M. A. Mihalyo, H. L. Aguila, R. S. Mittler, A. T. Vella, and A. J. Adler. 2008. Self-antigen prevents CD8 T cell effector differentiation by CD134 and CD137 dual costimulation. J. Immunol. 181: 7728-7737.
62. Jenkins, M. K., and R. H. Schwartz. 1987. Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J. Exp. Med. 165: 302-319.
63. Macian, F., F. Garcia-Cozar, S. H. Im, H. F. Horton, M. C. Byrne, and A. Rao. 2002. Transcriptional mechanisms underlying lymphocyte tolerance. Cell 109: 719-731.
64. DeSilva, D. R., K. B. Urdahl, and M. K. Jenkins. 1991. Clonal anergy is induced in vitro by T cell receptor occupancy in the absence of proliferation. J. Immunol. 147: 3261-3267.
65. + T cells. J. Exp. Med. 186: 239-245.
66. + T cells pass through an effector phase during the process of in vivo tolerance induction. J. Immunol. 170: 3945-3953.
67. Mihalyo, M. A., A. D. Doody, J. P. McAleer, E. C. Nowak, M. Long, Y. Yang, and A. J. Adler. 2004. In vivo cyclophosphamide and IL-2 treatment impedes self-antigen-induced effector CD4 cell tolerization: implications for adoptive immunotherapy. J. Immunol. 172: 5338-5345.