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Regulation of T Cell Activation by CD28 and CTLA4

  • Patricia J. Noel
  • Lawrence H. Boise
  • Craig B. Thompson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 406)

Abstract

T cell activation is initiated by engagement of the T cell receptor (TCR)-CD3 complex by antigen displayed by major histocompatibility complex (MHC) molecules expressed on the surface of an antigen presenting cell (APC). However, under most circumstances, this initial signal is insufficient to induce a proliferative response. TCR engagement in the absence of a second or costimulatory signal can lead to a state of anergy or cell death1. CD28 is a T cell surface receptor capable of providing this critical second signal following ligation of the B7 family of counter-receptors that are expressed on APCs2,3. This interaction provides not only proliferative signals, but also crucial survival signals that are important for both initiation and maintenance of an immune response4,5.

Keywords

Major Histocompatibility Complex Programme Cell Death Cell Death Pathway Immune Homeostasis Wildtype Mouse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    R.H. Schwartz, A cell culture model for T Lymphocyte clonal anergy, Science. 248: 1349 (1990).PubMedCrossRefGoogle Scholar
  2. 2.
    C.D. Gimmi, G.J. Freeman, J.G. Gribben, K. Sugita, A.S. Freedman, C. Morimoto, and L.M. Nadler, B-cell surface antigen B7 provides a costimulatory signal that induces T cells to proliferate and secrete interleukin 2, Proc. Natl. Acad. Sci. USA 88: 6575 (1991).PubMedCrossRefGoogle Scholar
  3. 3.
    N.K. Damle, L.V. Doyle, L.S. Grosmaire, and J.A. Ledbetter, Differential regulatory signals delivered by antibody binding to the CD28 (Tp 44) molecule during the activation of human T lymphocytes, J. Immunol. 140: 1753 (1988)PubMedGoogle Scholar
  4. 4.
    J.M. Green, P.J. Noel, A.I. Sperling, T.L. Walunas, G.S. Gray, J.A. Bluestone, and C.B. Thompson, Absence of B7-dependent responses in CD28- deficient mice, Immunity. 1: 501 (1994).PubMedCrossRefGoogle Scholar
  5. 5.
    Y. Shi, L.G. Radvanyi, A. Sharma, P. Shaw, D.R. Green, R.G. Miller, and G.B. Mills, CD28-mediated signaling in vivo prevents activation-induced apoptosis in the thymus and alters peripheral lymphocyte homeostasis, The Journal of Immunology. 155:1829 (1995).Google Scholar
  6. 6.
    T. Lindsten, C.H. June, J.A. Ledbetter, G. Stella, and C.B. Thompson, Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway, Science. 244: 339 (1989).CrossRefGoogle Scholar
  7. 7.
    C.B. Thompson, T. Lindsten, J.A. Ledbetter, S.L. Kunkel, H.A. Young, S.G. Emerson, J.M. Leiden, and C.H. June, CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines, Proc. Natl. Acad. Sci. USA. 86: 1333 (1989).PubMedCrossRefGoogle Scholar
  8. 8.
    L.H. Boise, A.J. Minn, P.J. Noel, C.H. June, M. Accavitti, T. Lindsten, and C.B. Thompson, CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-xL, Immunity. 3: 87 (1995).PubMedCrossRefGoogle Scholar
  9. 9.
    D. Kabelitz and S. Wesselborg, Life and death of a superantigen-reactive human CD4 + T cell clone: staphylococcal enterotoxins induce death by apoptosis but simultaneously trigger a proliferative response in the presence of HLA-DR+ antigen-presenting cells, International Immunology. 4: 1381 (1992).PubMedCrossRefGoogle Scholar
  10. 10.
    H. Groux, D. Monte, B. Plouvier, A. Capron, and J.-C. Ameisen, CD3-mediated apoptosis of human medullary thymocytes and activated peripheral T cells: respective roles of interleukin-1, interleukin-2, interferon-y and accessory cells, Eur. J. Immunol. 23: 1623 (1993).PubMedCrossRefGoogle Scholar
  11. 11.
    D.J. Veis, C.L. Sentman, E.A. Bach, and S.J. Korsmeyer, Expression of the Bel- 2 protein in murine and human thymocytes and in peripheral T lymphocytes, The Journal of Immunology. 151: 2546 (1993).PubMedGoogle Scholar
  12. 12.
    K-i. Nakayama, K. Nakayama, I. Negishi, K. Kuida, Y. Shinkai, M.C. Louie, L.E. Fields, P.J. Lucas, V. Stewart, F.W. Alt, and D.Y. Loh, Disappearance of the lymphoid system in Bcl-2 homozygous mutant chimeric mice, Science. 261: 1584 (1993).PubMedCrossRefGoogle Scholar
  13. 13.
    C.M. Chleq-Deschamps, D.P. LeBrun, P. Huie, D.P. Besnier, R.A. Warnke, R.K. Sibley, and M.L. Cleary, Topographical dissociation of BCL-2 messenger RNA and protein expression in human lymphoid tissues, Blood. 81: 293 (1993).PubMedGoogle Scholar
  14. 14.
    P.J. Noel, L.H. Boise, J.M. Green, and C.B. Thompson, CD28 costimulation prevents cell death during primary T cell activation, submitted. (1995).Google Scholar
  15. 15.
    C. Klas, K.-M. Debatin, R.R. Jonker, and P.H. Krammer, Activation interferes with the APO-1 pathway in mature human T-cells, International Immunology. 5: 625 (1993).PubMedCrossRefGoogle Scholar
  16. 16.
    B.C. Trauth, C. Klas, A.M.J. Peters, S. Matzku, P. Möller, W. Falk, K.-M. Debatin, P.H. Krammer, Monoclonal antibody-mediated tumor regression by induction of apoptosis, Science. 245: 301 (1989).PubMedCrossRefGoogle Scholar
  17. 17.
    N. Itoh, S. Yonehara, A. Ishii, M. Yonehara, S.-I. Mizushima, M. Sameshima, A. Hase, Y. Seto, and S. Nagata, The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis, Cell. 66: 233 (1991).PubMedCrossRefGoogle Scholar
  18. 18.
    S. Nagata and P. Golstein, The Fas death factor, Science. 267: 1449 (1995).PubMedCrossRefGoogle Scholar
  19. 19.
    K. Harper, C. Balzano, E. Rouvier, M.-G. Mattéi, M.-F. Luciani, and P. Golstein, CTLA-4 and CD28 activated lymphocyte molecules are closely related in both mouse and human as to sequence, message expression, gene structure, and chromosomal location, The Journal of Immunology. 147: 1037 (1991).PubMedGoogle Scholar
  20. 20.
    J.-F. Brunet, F. Denizot, M.-F. Luciani, M. Roux-Dosseto, M. Suzan, M.-G. Mattei, and P. Golstein, A new member of the immunoglobulin superfamily- CTLA-4, Nature. 328: 267 (1987).PubMedCrossRefGoogle Scholar
  21. 21.
    T. Lindsten, K.P. Lee, E.S. Harris, B. Petryniak, N. Craighead, P.J. Reynolds, D.B. Lombard, G.J. Freeman, L.M. Nadler, G.S. Gray, C.B. Thompson, and C.H. June, Characterization of CTLA-4 structure and expression on human T cells, The Journal of Immunology. 151: 3489 (1993).PubMedGoogle Scholar
  22. 22.
    G.J. Freeman, D.B. Lombard, C.D. Gimmi, S.A. Brod, K. Lee, J.C. Laning, D.A. Hafler, M.E. Dorf, G.S. Gray, H. Reiser, C.H. June, C.B. Thompson, and L.M. Nadler, CTLA-4 and CD28 mRNA are coexpressed in most T cells after activation: expression of CTLA-4 and CD28 mRNA does not correlate with the pattern of lymphokine production, The Journal of Immunology. 149: 3795 (1992).PubMedGoogle Scholar
  23. 23.
    T.L. Walunas, D.J. Lenschow, C.Y. Bakker, P.S. Linsley, G.J. Freeman, J.M. Green, C.B. Thompson, and J.A. Bluestone, CTLA-4 can function as a negative regulator of T cell activation, Immunity. 1: 405 (1994).PubMedCrossRefGoogle Scholar
  24. 24.
    P.S. Linsley, J.L. Greene, P. Tan, J. Bradshaw, J.A. Ledbetter, C. Anasetti, and N.K. Damle, Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes, J. Exp. Med. 176: 1595 (1992).PubMedCrossRefGoogle Scholar
  25. 25.
    P.S. Linsley, W. Brady, M. Urnes, L.S. Grosmaire, N.K. Damle, and J.A. Ledbetter, CTLA-4 is a second receptor for the B cell activation antigen B7, J. Exp. Med. 174: 561 (1991).PubMedCrossRefGoogle Scholar
  26. 26.
    J.G. Gribben, G.J. Freeman, V.A. Boussiotis, P. Rennert, C.L. Jellis, E. Greenfield, M. Barber, V.A. Restivo, Jr., X. Ke, G.S. Gray, and L.M. Nadler, CTLA4 mediates antigen-specific apoptosis of human T cells, Proc. Natl. Acad. Sci. USA. 92: 811 (1995).PubMedCrossRefGoogle Scholar
  27. 27.
    P. Waterhouse, J.M. Penninger, E. Timms, A. Wakeham, A. Shahinian, K.P. Lee, C.B. Thompson, H. Griesser, and T.W. Mak, Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4, Science. 270: 985 (1995).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Patricia J. Noel
    • 1
  • Lawrence H. Boise
    • 1
  • Craig B. Thompson
    • 1
    • 2
  1. 1.Department of MedicineGwen Knapp Center for Lupus and Immunology ResearchUSA
  2. 2.Howard Hughes Medical Institute Department of Molecular Genetics and Cell BiologyThe University of ChicagoChicagoUSA

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