THE IMMUNOBIOLOGY OF HIV INDUCED T-CELL DYSFUNCTION

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To understand what causes immune collapse seen in AIDS, we are investigating the functional effects of HIV and envelope on T-cell function in vitro. We have found that HIV, in addition to inhibiting T- cell function, has potent stimulatory activity on T-cells when presented simultaneously with regents which trigger the T-cell receptor. Envelope proteins potentiate both T-cell proliferation and IL-2 production. This "costimulatory" activity appears to be most active on naive peripheral T- cells and may explain the immune activation seen in both the CD4 and CD8 subsets of T-cells in HIV infected individuals. We are currently asking whether HIV mediated costimulation can induce abnormal cytokine regulation which is responsible for immune dysfunction. The results indicate that virus mediated signals in the course of HIV infection may lead to both viral inhibitory and costimulatory effects which together disrupt the normal balanced function of the immune system leading to AIDS. These studies are important to understanding the immunopathogenesis of HIV and to evaluating the biological effects of vaccines based on whole HIV and recombinant envelope proteins.