Preferential Apoptosis of HIV-1-Specific CD4+ T Cells

In contrast to other viral infections such as CMV, circulating frequencies of HIV-1-specific CD4 + T cells in peripheral blood are quantitatively diminished in the majority of HIV-1-infected individuals. One mechanism for this quantitative defect is preferential infection of HIV-1-specific CD4 + T cells, although + T cells are infected. Apoptosis has been proposed as an important contributor to the pathogenesis of CD4 + T cell depletion in HIV/AIDS. We show here that, within HIV-1-infected individuals, a greater proportion of ex vivo HIV-1-specific CD4 + T cells undergo apoptosis compared with CMV-specific CD4 + T cells (45 vs 7.4%, respectively, p + T cells correlates with viral load and disease progression, and highly active antiretroviral therapy abrogates these differences. The data support a mechanism for apoptosis in these cells similar to that found in activation-induced apoptosis through the TCR, resulting in oxygen-free radical production, mitochondrial damage, and caspase-9 activation. That HIV-1 proteins can also directly enhance activation-induced apoptosis supports a mechanism for a preferential induction of apoptosis of HIV-1-specific CD4 + T cells, which contributes to a loss of immunological control of HIV-1 replication.