THE IMMUNOBIOLOGY OF HIV INDUCED T-CELL AND MONOCYTE DYSFUNCTION

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To understand what causes immune collapse associated with AIDS, we are studying the effects of HIV and its envelope on T-cell and macrophage function in vitro. We have observed that HIV has both inhibitory and stimulatory activities on T-cell and macrophage function when presented simultaneously with reagents which trigger these cells. The cell activation marker CD26 has been shown to play an important role in monocytotropic virus entry and appears to contribute to cell dysfunction and cell priming for apoptosis. We examined the effects of HIV infection on cytokine secretion (IL-10, IL-12, and TNF) in macrophages. Virus infection alone does not induce cytokine secretion but indirectly modulates factor production depending on the primed status of the cell. Our results support a model of pathogenesis in which immune dysfunction is caused by both direct viral effects and indirect effects mediated by cytokines. In the course of these studies, we reported that secretion of the cytokine IL-12 involves coordinated expression of both the p40 and p35 chains of IL-12. Studies on the effects of HIV and cytokines on immune cell function is important to understanding immunopathogenesis of HIV and to evaluating the biological effects of AIDS and vaccine therapies. Hayes, M.P., Wang, J., and Norcross, M.A. Regulation of Interleukin-12 expression in human monocytes: selective priming by interferon-gamma of lipopolysaccharide-inducible p35 and p40 genes. Blood 1995; 86: 646-650.