Homeostatic regulation of CD8(+) T cells after antigen challenge in the absence of Fas (CD95)

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) alpha beta 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 alpha beta 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 Tcells 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 celIs. 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.