HOMEOSTATIC REGULATION OF CD8(-CELLS AFTER ANTIGEN CHALLENGE IN THE ABSENCE OF FAS (CD95)() T)

The role of Fas in the homeostatic regulation of CD8(+) T cells after antigen challenge was analyzed in the murine model of lymphocytic chor iomeningitis virus (LCMV) infection. Mice homozygous for the lpr mutat ion 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) w ere used. Five main results emerged: first, development of lymphadenop athy and of CD4(-)CD8(-) double-negative B220(+) T cells in lpr mice w as not inhibited by the alpha beta TCR transgenes; second, tolerance i nduction and peripheral deletion of CD8(+) T cells induced by LCMV gly coprotein 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 transg enic T cells expressing Fas; fourth, in vivo activated CD8(+) effector T cells from TCR transgenic and TCR-lpr/lpr mice were equally suscept ible 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(-) dou ble-negative T celIs. Taken together, these data suggest that the home ostatic regulation of CD8(+) T cells after antigen challenge in vivo i s regulated by mechanisms that do not require Fas.