Kinetics of T lymphocyte apoptosis and the cellular immune response in SIVmac239-infected rhesus macaques.

BACKGROUND: Although increased apoptosis is a central feature of AIDS, little is known about its kinetics or relationship to the early host response in acute HIV/SIV infection. METHODS: Ex vivo apoptosis in freshly isolated peripheral blood and lymph node lymphocytes was monitored longitudinally in SIVmac239-infected rhesus macaques by flow-cytometric detection of active caspase-3, cleaved poly (ADP-ribose) polymerase, and fragmented DNA. RESULTS: Increased apoptosis of multiple lymphocyte subsets was observed in the first 2 weeks following SIV infection. Apoptosis of CD4+ T lymphocytes was of low magnitude but peaked earlier than other T lymphocyte subsets. A 10- to 36-fold increase in CD8+ T lymphocyte apoptosis coincided temporally with onset of the SIV-specific cellular immune response and enrichment of caspase-3-positive cells within recently proliferating, activated CD8+ T lymphocytes. CONCLUSIONS: The virus-specific T lymphocyte response to primary infection and generalized non-specific immune activation contribute to the pathogenesis of apoptosis in acute SIV infection.