INFECTION AND APOPTOTIC CELL-DEATH OF CD4+ T-CELLS DURING AN IMMUNE-RESPONSE TO HIV-1-PULSED DENDRITIC CELLS

Interacting dendritic cells and helper CD4(+) lymphocytes form a microenvironment that is permissive for HIV-1 replication. The virus need only be pulsed initially onto the dendritic cells, which then transfer HIV-1 to the lymphocytes that are responding to presented antigens or superantigens. We have pursued underlying mechanisms in this system, because it provides a model for the infection of antigen-reactive, primary T cells. Pulsing the T cells with HIV-1 results in much less of a subsequent infection than does pulsing the dendritic cells. The latter pulse occurs effectively in the presence of AZT. Direct examination of the interacting dendritic cells and T cells reveals extensive production of p24 by many of the lymphocytes, including syncytia. The majority of the responding T cells die during the coculture. Apoptosis accounts for much of this death as revealed by in situ nick translation assays for DNA endonucleolysis, and hypodiploid profiles on staining with DNA-binding dyes. Therefore the microenviromnent that is generated between antigen-presenting dendritic cells and T cells reveals the cytopathic potential of HIV-1, because there is such extensive and rapid death by apoptosis of antigen-reactive T cells.