CD95-induced apoptosis contributes to loss of primed/memory but not resting/naive T cells in children infected with human immunodeficiency virus type 1

Increased apoptosis of uninfected CD4+ T cells is involved in CD4+ T cell depletion in HIV-1+ individuals. Recently, a progressive loss of resting naive T cells has been shown during the asymptomatic stage of HIV infection in children and adults. The CD95 receptor/ligand system is a key regulator of T cell apoptosis. To elucidate the role of this system in the depletion of resting naive T cells, we studied expression of CD95 and sensitivity toward CD95-triggered apoptosis in T cell subsets defined by CD45 (leukocyte common antigen) isoforms and CD62L (lymphocyte homing receptor L- selectin) in a cohort of HIV-1+ children. In patients and healthy control subjects the level of CD95 expression increased from resting/naive (L- selectin(bright) CD45RA+) T cells to primed/memory (CD45RO+ CD45RA+) T cells. In HIV-1+ children the susceptibility of peripheral blood T cells for CD95-mediated apoptosis also increased with progressive differentiation toward printed/memory T cells. Resting/naive T cells were resistant to spontaneous and anti CD95-induced apoptosis. Loss of naive (CD45RA+ CD45RO+) T cells in HIV-1+ patients in vivo was found to be paralleled by an increase in the percentage of CD95(high) T cells as well as an increase in anti CD95-induced apoptosis of CD4+ and CD8+ T cells. We conclude that loss of naive unprimed T cells during the asymptomatic phase of HIV-1 infection is caused by continuous generation o[' primed cells that exhibit increased sensitivity toward CD95 mediated apoptotic cell death in vitro.