Abstract
The role of Fas in the homeostatic regulation of CD8^+^ T cells after antigen challenge was analyzed in the murine model of lymphocytic choriomeningitis virus (LCMV) infection. Mice homozygous for the lpr mutation and carrying T cell receptor (TCR) αβ transgenes specific for the LCMV glycoprotein peptide aa 33–41 in the context of H‐2D^b^ were used. Five main results emerged: first, development of lymphadenopathy and of CD4^−^CD8^−^ double‐negative B220^+^ T cells in lpr mice was not inhibited by the αβ TCR transgenes; second, tolerance induction and peripheral deletion of CD8^+^ T cells induced by LCMV glycoprotein peptide injection was independent of Fas expression; third, clonal down‐regulation of Fas‐deficient TCR‐transgenic CD8^+^ T cells after acute LCM virus infection was identical to the decline of transgenic T cells expressing Fas; fourth, in vivo activated CD8^+^ effector T cells from TCR transgenic and TCR‐lpr/lpr mice were equally susceptible to activation‐induced cell death in vitro; and fifth, transgenic effector T cells from lpr/lpr mice were cleared in the declining phase of the immune response in vivo without giving rise to CD4^−^CD8^−^ double‐negative T cells. Taken together, these data suggest that the homeostatic regulation of CD8^+^ T cells after antigen challenge in vivo is regulated by mechanisms that do not require Fas.