This is a combined experimental and clinical program to understand the role of cell mediated immunity in HIV-1 and Mycobacterium tuberculosis infections and to evaluate cytokine immunotherapy in patients with AIDS and Tuberculosis. All segments will utilize material collected from patients with 1. Various stages of HIV-1 infection from asymptomatic seropositives to advanced AIDS, both adult and childhood disease, 2. Pulmonary and extrapulmonary Tuberculosis, 3. AIDS with Tuberculosis. Patients will be followed on the wards and OPD of the hospital of The Rockefeller University and cared for by our clinical investigators. In vitro studies will be carried out in the adjacent facilities of The Laboratory of Cellular Physiology and Immunology. Using primary cells we will explore the functions of natural killer cells (NK), lymphokine activated killer cells (LAK), CD4+ and CD8+ cytotoxic T cells and monitor whether any of these cell types, especially after cytokine therapy in situ recognize monocyte infected with HIV-1 or M. tuberculosis. We will evaluate the expression of cytokine and cytokine mRNAs in circulating cells and the production of cytokines by cultured cells obtained from the blood, bone marrow and bronchoalveolar lavage. We will evaluate mechanisms whereby patients fail to generate a delayed type skin reaction (including HIV-1 Ag) and the reasons that recombinant huIL-2 is able to restore these reactions and to improve the clinical status of some AIDS patients with Candidasis and other opportunistic infections. We wish to understand the status of cell mediated immunity in patients with tuberculosis. This includes the recognition of infected monocytes by specific and non-specific cytotoxic cell populations and the role of cytokines in the immunopathology and in the destruction of M. tuberculosis. We will explore the roles of rIFNgamma and IL-2 in enhancing resistance to M. tuberculosis and the influence of the selective TNFalpha inhibitor - Thalidomide - in decreasing the systemic manifestations of the disease. We will also compare the above parameters as they are expressed in patients with HIV-1 infection, tuberculosis and patients with both AIDS and tuberculosis. This comparison should lead to important insights into the process of opportunistic infections and enable us to immuno modulate these patients to improve their clinical prognosis.
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