Induction of CD56+ T cells after prolonged activation of T cells in vitro: A possible mechanism for CD4+ T-cell depletion in acquired immune deficiency syndrome patients

The pathogenic mechanisms responsible for depletion of CD4+ T cells in aquired immune deficiency syndrome (AIDS) are not fully understood. Systemic immune activation mediated by persistent infection of human immunodeficiency virus (HIV) seems to be one of the predictors of disease progression. We predicted that certain lymphocytes responsible for CD4+ T-cell depletion could be induced in patients during prolonged activation of lymphocytes. Therefore, we have established an in vitro long-term culture system for peripheral blood mononuclear cells with PHA-P stimulation and Herpesvirus saimiri infection, and examined what types of cells having strong cytotoxic activity to be emerged under the activated conditions. We observed that percentage of CD56+ T cells was gradually increased in cultures from 30 days after stimulation and exhibited a cytotoxic activity against both autologous and allogeneic targets. Interestingly, HIV-1 infection enhanced the susceptibility of CD4+ T cells to their cytotoxic effectors, and CD4+ T cells from HIV-1–infected individuals showed decreased survival rate in the presence of autologous CD56+ T cells. These findings raised the possibility that induction of autoreactive CD56+ T cells in consequence of immune activation might be contributed to the depletion of CD4+ T cells in HIV-1–infected patients.