Costimulatory pathways mediate monocyte-dependent lymphocyte apoptosis in HIV

Examination of annexin V binding, an indicator of early apoptosis, on lymph ocytes from HIV+ people immediately after isolation showed that both CD4(+) and CD8(+) T cells were apoptotic, whereas B cell apoptosis was induced ma inly after incubation. CD8(+) T cell apoptosis correlated with fewer CD4(+) T cells, but not the level of viremia. To determine potential mechanisms f or apoptosis, we examined Fast expression, which was dramatically elevated on CD14(+) monocytes; however, antibody to Fast did not reproducibly inhibi t apoptosis. Rather, CD8(+) T cell apoptosis was caused by antigen-presenti ng cells because removal of monocytes or addition of antibodies to CD80 and CD86 reduced apoptosis. B cell apoptosis also involved costimulatory signa ls delivered by T cells but not monocytes. A unique CD8(bright)CD28(dim) T cell population died after costimulation by monocytes. Because this populat ion was increased in patients with undetectable viremia, abnormal antigen-p resenting cells may contribute to continued CD8(+) T cell exhaustion by ind ucing apoptosis, (C) 1999 Academic Press.