T-LYMPHOCYTE DOWN-REGULATION AFTER ACUTE VIRAL-INFECTION IS NOT DEPENDENT ON CD95 (FAS) RECEPTOR-LIGAND INTERACTIONS

Infection of mice with lymphocytic choriomeningitis virus (LCMV) cause s a major expansion of CD8(+) T cells followed by a period of immune d ownregulation that coincides with the induction of lymphocyte apoptosi s in the mouse spleen. CD95 (Fas) and its ligand are important for reg ulating peripheral T-lymphocyte numbers and can mediate apoptosis of m ature T lymphocytes. We infected CD95- and CD95L-deficient mice (lpr a nd gld, respectively) with LCMV to determine if the immune downregulat ion that occurred following resolution of the LCMV infection was due t o a CD95-dependent apoptotic mechanism. Lymphocytes from LCMV-infected lpr and gld mice were capable of normal T-cell expansion and cytolyti c function but were, in contrast to activated cells from normal virus- infected mice, relatively more resistant to T-cell receptor-induced ap optosis in vitro. However, in vivo there were significant numbers of a poptotic cells in the spleens of lpr and gld mice recovering from the infection, and the T-cell number and cytolytic activity decreased to n ormal postinfection levels. Thus, CD95 is not required for the immune downregulation of the CDS'-T-lymphocyte response following acute LCMV infection.