DEVELOPMENTAL IMMUNOLOGY RESEARCH

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The primary objective of component C of RFA-NIH-92-AI-14 is to "provide investigators with resources to answer clinically relevant questions with emphasis on utilizing specimens generated from ACTG protocols". The present proposal will address this objective by providing human and logistic resources for the evaluation of immune functions in patients enrolled in AIDS clinical trials at Meharry Medical College. HIV compromises the immune system in two major ways: Severe depletion of CD4+ T-cells and decline in T-helper (th) cell functions. CD4+ cell counts are the most commonly used immunological parameter for the evaluation of patients with HIV/AIDS. However, the loss of Th cell functions precedes and is independent of the decline in CD4+ cell counts. Since there is a connection between the impairment of Th cell functions and the clinical evolution of HIV/AIDS, we propose the early characterization and evaluation of specific and non-specific immune responses as necessary tools for diagnosis and for monitoring medical intervention in HIV/AIDS. The objective of this component is the strengthen our existing human and laboratory resources to provide support for research in immunology of AIDS and to develop and provide less commonly used research tools to look at functional immune parameters in human subjects involved in ACTU protocols at Meharry. These functional parameters are: 1) Specific immune functions (memory responses). a) cellular immunity: lymphocyte responses to recall antigens (i.e. HIV antigens and mitogens), capacity of human cytotoxic lymphocytes to kill target cells expressing or carrying HIV antigens, b) antibody responses: human production of specific antibody isotypes against HIV antigens, or other relevant antigens, and evaluation of T-helper activity in the specific antibody response to Tetanus toxoid in vivo. 2) Non-specific immune responses. a) phagocytic cell function: study of the metabolic activity of phagocytic cells by chemiluminescence, b) lymphocyte activation: flowcytometry analyses of the expression and distribution of lymphocyte markers for activation and identification of lymphocyte subsets associated with the progression of HIV infection/AIDS, c) Humoral parameters for cellular and humoral immune functions: quantitation of cytokines (i.e. IL-1 alpha and beta, IL-2, IL-4, IL-6, TNF alpha and beta, gammaIFN), complement fractions, neopterin, beta2-microglobulin and others which may become relevant in HIV infection.