APOPTOSIS OCCURS PREDOMINANTLY IN BYSTANDER CELLS AND NOT IN PRODUCTIVELY INFECTED-CELLS OF HIV-INFECTED AND SIV-INFECTED LYMPH-NODES

Although 13 years have passed since identification of human immunodefi ciency virus-1 (HIV-1) as the cause of AIDS, we do not yet know how HI V kills its primary target, the T cell that carries the CD4 antigen. W e and others have shown an increase in the percentage of apoptotic cel ls among circulating CD4(+) (and CD8(+)) T cells of HIV-seropositive i ndividuals and an increase in frequency of apoptosis with disease prog ression. However, it is not known if this apoptosis occurs in infected or uninfected T cells. We show here, using in situ labelling of lymph nodes from HIV-infected children and SIV-infected macaques, that apop tosis occurs predominantly in bystander cells and not in the productiv ely infected cells themselves. These data have implications for pathog enesis and therapy, namely, arguing that rational drug therapy may inv olve combination agents targeting viral replication in infected cells and apoptosis of uninfected cells.