Our research is focused on identifying key regulatory events that influence T cell mediated immunity in vivo. This includes an analysis of cytokine regulation of effector cell development and the functional activities of T cells that culminate in tissue damage. These studies are conducted primarily in the mouse vascularized cardiac allograft model. Emphasis is placed on the role of inductive cytokines (IL-12, IFN gamma, IL-4, IL-10, IL-6 and TGF beta) which influence the balance between Th1, Th2, and Th17 helper T lymphocytes and the role of the CD40 - CD40 ligand costimulatory pathway in the subsequent development of deleterious versus tolerogenic immune responses. We have adapted the vascularized cardiac transplant model for in situ gene transfer studies to assess the effects of local expression of immunosuppressive genes on systemic immune responses that lead to acute or chronic allograft rejection.