APOPTOSIS OF CD4(-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION - CORRELATION WITH CLINICAL PROGRESSION, VIRAL LOAD, AND LOSS OF HUMORAL IMMUNITY() AND CD19(+) CELLS DURING HUMAN)

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 ev ent to HIV pathogenesis and disease progression, apoptosis in CD4(+) T lymphocytes and CD19(+) B lymphocytes, viral load, and neutralizing a ntibody titers were assayed in HIV-l-infected slow progressors and pro gressors. A correlation was found between progressive disease and apop tosis of CD4(+) T cells. The extent of apoptosis in CD4(+) cells was s imilar in slow progressors and seronegative control subjects. By contr ast, we found elevated levels of B-cell apoptosis in all HIV-1-infecte d individuals compared with seronegative control subjects, with a tend ency toward increased levels of apoptosis with progressive disease. Ap optosis in CD4(+) T cells and CD19(+) B cells correlated with viral RN A levels in plasma. Furthermore, higher rates of B-cell apoptosis were observed in individuals with poor neutralizing activity against a pan el of six clinical HIV-1 isolates. From these results we conclude that the extent of apoptosis in cultured CD4(+) cells and CD19(+) cells ap pears to parallel the decline in CD4 cell counts in infected individua ls. The finding of a relation between apoptosis in B cells and poor ne utralizing capacity suggests that apoptosis may be related to loss of immune function. A role for apoptosis in the pathogenesis of AIDS is a lso supported by the strong correlation between viral load and rates o f apoptosis in CD4(+) T cells. (C) 1997 Academic Press.