DIMINISHED SPONTANEOUS APOPTOSIS IN LYMPHOCYTES FROM HUMAN IMMUNODEFICIENCY VIRUS-INFECTED LONG-TERM NONPROGRESSORS

The relationship between peripheral lymphocyte apoptosis and human imm unodeficiency virus disease progression was studied in infected subgro ups with distinct profiles of progression. Longterm nonprogressors (LT NP) and seronegative controls had levels of spontaneous apoptosis sign ificantly lower than those for recent seroconverters who had CD4 cell counts similar to those of nonprogressors but with a high likelihood o f disease progression. Lymphocytes from nonprogressors and seronegativ e controls also showed negligible spontaneous caspase-3 activity, a bi ochemical indicator for apoptosis, whereas early progressors exhibited substantial activity. In contrast, when activated with mitogens, the lymphocytes from both LTNP and progressors displayed indistinguishable levels of heightened apoptosis, Spontaneous apoptosis and plasma vire mia levels correlated positively in progressors, but not in LTNP, Thes e findings demonstrate that increased lymphocyte apoptosis is evident prior to CD4 T cell decline and that LTNP are relatively resistant to the factors that induce accentuated levels of spontaneous but not mito gen-induced cell death.