A specific T-cell subset with CD4+/CD38− markers derived from HIV-1 carriers induces apoptosis in healthy donor-derived T-lymphocytes

Apoptosis is an important mechanism of human immunodeficiency virus type 1 (HIV-1)-induced T-cell depletion. Our recent findings revealed mitogenic stimulation-dependent apoptosis induction in healthy donor-derived peripheral blood T-lymphocytes after adsorption with defective HIV-1 particles through acquirement by a subset of CD4+/CD38− cells of specific killer function. Based on these in vitro observations, we have extended the significance of this killing activity of CD4+/CD38− cells directly derived from HIV-1 carriers. The CD4+/CD38− cells from HIV-1-positive individuals showed significantly higher cell-killing activities than those from HIV-1-negative donors by co-culture with allogeneic resting T-cells after mitogenic stimulation. Furthermore, most of the samples induced apoptosis in a Fas-dependent manner. Thus, it is suggested that HIV-1 infection-related apoptosis is triggered by inappropriate activation of a certain resting T-cell subset, presumably due to adsorption with HIV-1 particles.