Apoptosis of CD4(+) and CD19(+) cells during human immunodeficiency virus type 1 infection - correlation with clinical progression, viral load, and loss of humoral immunity

Enhanced rates of programmed cell death (apoptosis) have been detected in T cells and B cells from human immunodeficiency virus type 1 (HIV-l)-infected individuals. To evaluate the possible relevance of this event to HIV pathogenesis and disease progression, apoptosis in CD4(+) T lymphocytes and CD19(+) B lymphocytes, viral load, and neutralizing antibody titers were assayed in HIV-l-infected slow progressors and progressors. A correlation was found between progressive disease and apoptosis of CD4(+) T cells. The extent of apoptosis in CD4(+) cells was similar in slow progressors and seronegative control subjects. By contrast, we found elevated levels of B-cell apoptosis in all HIV-1-infected individuals compared with seronegative control subjects, with a tendency toward increased levels of apoptosis with progressive disease. Apoptosis in CD4(+) T cells and CD19(+) B cells correlated with viral RNA levels in plasma. Furthermore, higher rates of B-cell apoptosis were observed in individuals with poor neutralizing activity against a panel of six clinical HIV-1 isolates. From these results we conclude that the extent of apoptosis in cultured CD4(+) cells and CD19(+) cells appears to parallel the decline in CD4 cell counts in infected individuals. The finding of a relation between apoptosis in B cells and poor neutralizing capacity suggests that apoptosis may be related to loss of immune function. A role for apoptosis in the pathogenesis of AIDS is also supported by the strong correlation between viral load and rates of apoptosis in CD4(+) T cells. (C) 1997 Academic Press.