CD28-MEDIATED SIGNALING IN-VIVO PREVENTS ACTIVATION-INDUCED APOPTOSISIN THE THYMUS AND ALTERS PERIPHERAL LYMPHOCYTE HOMEOSTASIS

Activation of T lymphocytes can result in a functional immune response , anergy or apoptosis. Functional T cell activation requires the inter action of the TCR with Ag presented by MHC molecules on APC concurrent with appropriate interactions between cell surface accessory molecule s. interestingly, the level of CD28 expression is regulated during T c ell development as well as during T cell activation and proliferation, suggesting that CD28 could play a role in determining the outcome of activation of TCR during T cell ontogeny. We identify, herein, a novel function of murine CD28 in the regulation of activation-induced apopt osis in thymocytes. In vivo, or combined in vivo and in vitro treatmen t with mAbs to CD28 prevents apoptosis of CD4(+)CD8(+) thymocytes indu ced by Abs to the TCR complex. Prolonged administration of anti-CD28 A bs increased the number of both CD4(+)CD8(-) and CD4(-)CD8(+) T cells in the thymus, while the number of CD4(+)CD8(+) T cells is relatively unchanged. Furthermore, this treatment leads to a dramatic enlargement of peripheral lymphoid organs characterized primarily by the expansio n of B cells. The number of CD4(+)CD8(-) T cells in the spleen of anti -CD28-treated mice is also moderately increased, while the number of C D4(-)CD8(+) cells is relatively unchanged.