Acquire immunodeficiency syndrome (AIDS) is characterized by depressed cell-mediated immunity associated with Kaposi's sarcoma and/or opportunistic infections, usually found in homosexual males, I.V. drug abusers, hemophiliacs and Hatian immigrants. The depressed cell-mediated immunity is in paradox with the elevated levels of thymosin Alpha1, suggests a lack of precursors of T cell lineage/or and biologically inactive thymosin Alpha1. AIDS is considered a syndrome of immunodysregulation characterized by imbalance of ratios of helper/suppressor T cells phenotypes. In the autologous mixed lymphocyte reaction distinct T cell subsets respond to non T cells (T-non T AMLR) or activated T cells (T-T AMLR) and express distinct immunoregulatory functions. Interleukin1 produced by macrophages enhances the production of IL-2 in the AMLR. Therefore, we plan to study the AMLR, that is considered a basic model of immunoregulation, in AIDS. Furthermore, we will study the inductive influence of thymic epithelium and thymic factors on phenotypic and functional differentiation to delineate the level of T cell defect(s) in AIDS. Peripheral blood lymphocytes will be further separated into T cells, T cells subsets (latter by panning) and non T cells. T cells activated in T-non T AMLR will be used as stimulators in T-T AMLR. T cells activated in T-non T and T-T AMLR will be studied for helper/suppressor functions against T cell proliferation and B cell differentiation to immunoglobulin producing cells in plaque forming cell assay. The production of IL-2 (measured on IL-2 dependent T cell line) and influence the purified IL-2 on the AMLR will be studied. Adherent macrophages are stimulated with LPS and IL-1 activity is measured by thymocyte mitogenic assay. Various fractions of bone marrow and peripheral blood mononuclear cells will be incubated with cultured thymic epithelium, thymic culture supernatants, thymosin V and thymosin Alpha1 and examined for the expression of differentiation antigens using monoclonal antibodies and FACS analyzer, proliferative response to mitogens, AMLR and for immunoregulatory functions. These studies will help in understanding the cellular and molecular basis of immunodysregulation and the role of thymic epithelium and its products in T cell differentiation in AIDS, that might help in possible immunological interventions in the management of immunodeficiency in AIDS.
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