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Publication : CD28 costimulation is required for in vivo induction of peripheral tolerance in CD8 T cells.

First Author  Vacchio MS Year  2003
Journal  J Exp Med Volume  197
Issue  1 Pages  19-26
PubMed ID  12515810 Mgi Jnum  J:109348
Mgi Id  MGI:3628737 Doi  10.1084/jem.20021429
Citation  Vacchio MS, et al. (2003) CD28 costimulation is required for in vivo induction of peripheral tolerance in CD8 T cells. J Exp Med 197(1):19-26
abstractText  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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