Frequency of provirus-bearing CD4 super(+) cells in HIV type 1 infection correlates with extent of in vitro apoptosis of CD8 super(+) but not of CD4 super(+) cells

Lymphocytes from HIV-1-infected subjects undergo massive apoptosis when cultured in vitro, and this phenomenon might reflect pathogenetic mechanisms leading to immune dysfunction in vivo. However, (1) lymphocyte death is not restricted to CD4 super(+) cells but seems to involve predominantly CD8 super(+) cells, and (2) the same phenomenon occurs in other viral infections. Furthermore, it is not known whether a relationship exists between the HIV-1 burden and this type of cell death. In this work we sought to determine whether the HIV-1 provirus load correlates with the propensity to apoptosis of CD4 super(+) and CD8 super(+) cells. We studied 10 HIV-1-infected patients with CD4 super(+) cell counts above 500/mm super(3) and free of concomitant infections. We correlated the frequency of HIV-1-infected CD4 super(+) cells with the extent of culture-induced apoptosis as well as with the phenotype of the apoptotic lymphocytes. We found that the magnitude of apoptosis correlated with the frequency of HIV-1-infected CD4 super(+) cells (p = 0.0007), and that increasing viral load and apoptosis were associated with a shift to the selective death of CD8 super(+) cells. Our data support the view that, in addition to CD4 super(+) cell killing, another immunopathogenic effect of HIV might be that of priming CD8 super(+) cells to apoptosis. In vivo, this could eventually lead to the exhaustion of the cytotoxic T cell compartment.