HIV infected individuals show an increased pre-disposition to mycobacterial infection early (M. tuberculosis) and late (M. avium) in their course of disease. In vitro studies suggest that macrophage handling of mycobacteria is not impaired even in the presence of replicating HIV. It is likely that CD4+ cells play the pivotal role in the immune response perhaps in concert with gamma delta T cells which are known to proliferate in response to M. tuberculosis in vitro. It is possible that gamma delta T cells play a role in the immune response to M. avium, and that this infection is not manifest until late in disease when CD4+ cell function is not capable alone of controlling infection. The purpose of our proposal is to identify those defects in the T cell function in response to mycobacterial antigens by, 1) enumerating gamma delta T cells early and late in HIV infection, 2) comparing qualitative and quantitative T cell (CD4+ and gamma delta) responses with cells from subjects who are either tuberculin reactors, or who have a positive history of tuberculin reactivity early and late in HIV infection using in vitro systems of M. tuberculosis infected macrophages, 3) applying in vitro assays of M. avium infected macrophages in patients in early and late HIV infection, 4) studying the effect of therapeutic strategies on T cell responses to M. avium in infected individuals. The goal of our research is to characterize T cell defects which contribute to the pre-disposition to mycobacterial disease in HIV infected individuals. Insights into specific T cell dysfunction may assist in identifying individuals at risk for mycobacterial disease, developing immunomodulatory therapies, and assessing immunologic response to therapy.
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