Whereas ligation of CD28 is known to provide a critical costimulatory signal for activation of CD4 T cells, the requirement for CD28 as a costimulatory signal during activation of CD8 cells is less well defined. Even less is known about the involvement of CD28 signals during peripheral tolerance induction in CD8 T cells. In this study, comparison of T cell responses from CD28-deficient and CD28 wild-type H-Y–specific T cell receptor transgenic mice reveals that CD8 cells can proliferate, secrete cytokines, and generate cytotoxic T lymphocytes efficiently in the absence of CD28 costimulation in vitro. Surprisingly, using pregnancy as a model to study the H-Y–specific response of maternal T cells in the presence or absence of CD28 costimulation in vivo, it was found that peripheral tolerance does not occur in CD28KO pregnants in contrast to the partial clonal deletion and hyporesponsiveness of remaining T cells observed in CD28WT pregnants. These data demonstrate for the first time that CD28 is critical for tolerance induction of CD8 T cells, contrasting markedly with CD28 independence of in vitro activation, and suggest that the role of CD28/B7 interactions in peripheral tolerance of CD8 T cells may differ significantly from that of CD4 T cells.
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6 January 2003
Article|
December 23 2002
CD28 Costimulation Is Required for In Vivo Induction of Peripheral Tolerance in CD8 T Cells
Melanie S. Vacchio,
Melanie S. Vacchio
1Experimental Immunology Branch, National Cancer Institute
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Richard J. Hodes
Richard J. Hodes
1Experimental Immunology Branch, National Cancer Institute
2National Institute on Aging, National Institutes of Health, Bethesda, MD 20892
Search for other works by this author on:
Melanie S. Vacchio
1Experimental Immunology Branch, National Cancer Institute
Richard J. Hodes
1Experimental Immunology Branch, National Cancer Institute
2National Institute on Aging, National Institutes of Health, Bethesda, MD 20892
Address correspondence to M.S. Vacchio, Building 10, Rm. 4B10, 10 Center Dr., Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1360. Phone: 301-435-6461; Fax: 301-496-0887; E-mail: [email protected]
*
Abbreviations used in this paper: CTLA, CTL antigen; TCM, tissue culture medium.
Received:
August 15 2002
Revision Received:
September 25 2002
Accepted:
October 10 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2003
J Exp Med (2003) 197 (1): 19–26.
Article history
Received:
August 15 2002
Revision Received:
September 25 2002
Accepted:
October 10 2002
Citation
Melanie S. Vacchio, Richard J. Hodes; CD28 Costimulation Is Required for In Vivo Induction of Peripheral Tolerance in CD8 T Cells . J Exp Med 6 January 2003; 197 (1): 19–26. doi: https://doi.org/10.1084/jem.20021429
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