Emphasis on the study of HIV infection of T lymphocytes has skewed research on the pathogenesis of AIDS and development of novel therapeutic approaches. Direct and indirect effects of HIV infection of non-T cell targets, notably dendritic cells (DC), Langerhans cells (LC), and macrophages (M-phi) play an important role in the pathogenesis of AIDS and the immunopathobiology of HIV infection. However, there are significant technical challenges involved in working with non-T cell targets of HIV, owing chiefly to the fact that primary cell populations must be used that are extremely difficult to isolate, culture and analyze, and are often available in limiting numbers or purity. We have developed a series of state of the art approaches for the isolation, purification, culture, in vitro HIV infection and analysis of non-T cell targets of HIV infection. We will utilize these methods to study the immunological consequences of HIV infection in these cells. In addition, we will evaluate the effects of approved and experimental anti-HIV therapeutics on the immunological functions of these cells. Finally, we will develop methods to efficiently exploit the unique immunological properties of these cells to develop effective approaches for passive cellular immunological approaches to the treatment of HIV infection and AIDS. Specific objectives to be pursued include: 1. Optimization of methods for the use of DC to generate HIV specific cytotoxic T cells; 2. Development of improved methods for the isolation, culture, and analysis of DC; 3. Evaluation of the immunopharmacology and immunotoxicology of antiviral compounds of interest; 4. Evaluation of the effects of HIV infection and exposure to viral proteins on immunologic functions of non-T cells.
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