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 CD8brightCD28dimT 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.