Apoptotic T cell death in HIV/AIDS

Abstract

Apoptotic T cell death may play an important role in the progression of HIV infection to AIDS. Experimental observations suggest that T lymphocytes of HIV-infected individuals produce less type 1 cytokines (including IL-2 and IL-12) and more type 2 cytokines (including IL-10). Data have shown that type 1 cytokines reduce apoptotic death of HIV-infected lymphocytes induced in vitro by at least three different methods: gp120-CD4 cross-linking, CD3-TcR activation, and IL-2 deprivation. In contrast, type 2 cytokines have either no effect or enhance apoptotic death of lymphocytes of HIV-infected individuals. The model shown predicts that, whereas T lymphocytes of HIV-seronegative individuals are mostly in a resting situation and produce IL-2 upon antigenic stimulation, exposure of CD4 T cells to HIV or HIV products activate T cells for a second death-inducing stimulus, resulting in extensive apoptotic T cell death. These non-infectious interactions between CD4 cells and HIV or its products contribute to the depletion of CD4 T cells without the need for infection of such cells. This mechanism would result in pan-depletion of activated T cells expressing a broad spectrum of antigen specificities. The observation that type 1 cytokines are reduced, whereas type 2 cytokines are augmented in HIV infection accounts for the continuous and massive destruction of CD4 lymphocyte leading to the appearance of AIDS.