Costimulatory pathways mediate monocyte-dependent lymphocyte apoptosis in HIV

Examination of annexin V binding, an indicator of early apoptosis, on lymphocytes from HIV⁺ people immediately after isolation showed that both CD4⁺ and CD8⁺ T cells were apoptotic, whereas B cell apoptosis was induced mainly after incubation. CD8⁺ T cell apoptosis correlated with fewer CD4⁺ T cells, but not the level of viremia. To determine potential mechanisms for apoptosis, we examined FasL expression, which was dramatically elevated on CD14⁺ monocytes; however, antibody to FasL did not reproducibly inhibit apoptosis. Rather, CD8⁺ T cell apoptosis was caused by antigen-presenting cells because removal of monocytes or addition of antibodies to CD80 and CD86 reduced apoptosis. B cell apoptosis also involved costimulatory signals delivered by T cells but not monocytes. A unique CD8(bright)CD28(dim) T cell population died after costimulation by monocytes. Because this population was increased in patients with undetectable viremia, abnormal antigen-presenting cells may contribute to continued CD8⁺ T cell exhaustion by inducing apoptosis.