The immunosuppression inpatients with AIDS is often out of proportion to the level of CD4+ lymphocyte depletion. Moreover, for many of the infections in AIDS patients the monocyte-macrophage is the primary host defense cell. These observations, together with recent evidence that monocytes also are a target of HIV infection, suggest the possibility that the virus itself may induce defective monocyte function. Therefore, the focus of this laboratory has been monocyte dysfunction in AIDS. Our results indicate that HIV alters spontaneous and stimulated production of 0-2 a key reactive oxygen intermediate involved in oxygen-dependent cytotoxicity and tissue inflammatory changes. Preliminary results also indicate that uptake of HIV by mucosal M cells may be a mechanism of viral entry into the host. Relevant to vaccine development, we have found that IgA, but not IgG, antibodies to HIV are absent in the intestine. Experiments to determine whether HIV infection of monocytes alters B cell Ig secretion are in progress. We have shown that cytomegalovirus, the most common opportunistic infection in AIDS patients, impairs accessory cell function and stimulates tumor necrosis factor secretion. Our observations on the ability of GM-CSF to augment 0-2 production, cytotoxicity, and HLA-DR expression either in vitro or in vivo are clinically relevant to the ongoing trials of GM-CSF therapy in AIDS patients. Also, DNA restriction patterns of C. albicans from AIDs patients are similar to isolates from normal subjects; indicating that the immune response, as opposed to a specific genotype, is the critical factor in the development of candidiasis in patients. Therefore, we are investigating the mechanism of monocyte killing of Candida. Studies on the contribution of alveolar macrophages to the pulmonary inflammatory changes observed in AIDSs, endotoxic shock, and cystic fibrosis, to compare to the role of the alveolar macrophage in AIDS patients are in progress.
