LYMPHOCYTE APOPTOSIS DURING THE SILENCING OF THE IMMUNE-RESPONSE TO ACUTE VIRAL-INFECTIONS IN NORMAL, IPR, AND BCL-2-TRANSGENIC MICE

This report examines the mechanisms involved in the down-regulation of the immune response in acute viral infection and documents the presen ce of apoptotic lymphocytes in situ in the spleens of mice during the resolution of the immune response to acute lymphocytic choriomeningiti s virus infection Apoptotic cells were detected by an in situ nucleoti dyl transferase assay. Both T and B lymphocytes were shown to be dying in vivo, the latter in clusters. A biphasic occurrence of apoptosis d uring the course of the acute infection was observed with elevated lev els occurring at day 3 after infection and a second more pronounced pe ak at day II after infection, coincident with the decline of the cytot oxic T lymphocyte response and with the decrease in total splenic leuk ocyte number. Apoptosis in vivo was detected in 1pr mice, suggesting t hat Fas expression is not imperative for lymphocyte apoptosis in the c ontext of an acute viral infection. Apoptosis in situ and the decline of the T lymphocyte response to acute lymphocytic choriomeningitis vir us infection was unaffected by the enforced lymphocyte-directed expres sion of Bcl-2, a protein that blocks growth factor deprivation-induced apoptosis of lymphocytes in vitro. These results argue that the silen cing of the T cell response to acute infection may not be a result sim ply of growth factor deprivation. The susceptibility of activated T ce lls to apoptotic death, which has previously been associated with viru s-induced immune deficiency, may therefore also explain the en masse e limination of the expanded lymphocyte pool subsequent to an acute vira l infection.