The major focus of this proposal is the identification and characterization of those interleukins required for the growth and differentiation of suppressor T lymphocytes. Substantial insights have been gained concerning the normal growth and differentiative requirements for helper and cytolytic T cells and more recently for B cells, and identification of defects in these requirements have begun to clarify regulatory dysfunctions that underly clinical and experimental immune disease. In contrast, the soluble factors required for proliferation and growth of suppressor T cells are poorly understood, and certain observation suggest that these requirements may be unique in comparison to those of other T cell subsets. Thus, utilizing a recently developed suppressor T cell (Ts) constimulator assay three major objectives will be undertaken. First, interleukins required for Ts proliferation and effector function will be identified and characterized. Ts costimulators will be isolated by various biochemical technologies, characterized for proliferative and/or differentiative functions and examined for synergistic interactions. Second the nature and triggering requirements of the cell target(s) of Ts associated interleukins will be established. Target Ts cell populations will be isolated by various enrichment procedures, cellular and alloantigenic characteristics of stimulator cells in the Ts costimulator assay will be defined, and cloned Ts will be used to verify and quantitate Ts interleukin-target cell interactions. Third, the antigenic and cellular requirements for production of Ts interleukins will be determined. Cellular and antigenic conditions of Ts cofactor production in allogeneic cell mixtures will be defined, and used as a basis for hybridoma production of proliferative and differentiative Ts interleukins. This analysis of the array and interactions of interleukins important to Ts function is anticipated to produce insights fundamental to understanding both physiologic and disordered Ts regulation.
