Activation of T cells is a complex process involving cell membrane. Cytoplasmic and nuclear events. These events enable T cells to proliferate and exert their immunoregulatory function. The goal of these studies is to better understand the calcium-dependent pathway of T cell activation and define the effects of biologic agents used for the therapy of immune mediated renal diseases (glucocorticoids, cyclosporin A) and those mediators produced at the site of inflammation (prostaglandin E2, transforming growth factor-beta or TGF-beta) on T cell activation. Findings to date indicate that glucocorticoids inhibit IL-2 gene transcription by interfering with the binding of nuclear factors AP-1 and NF-AT on the human IL-2 promoter. Glucocorticoids inhibit both T cell antigen receptor and IL-2 receptor mediated proliferative signals (tyrosine phosphorylation, production of transcription factors, expression of lymphokine genes, Rb protein phosphorylation). Prostaglandin E2 also downregulates T cell activation and proliferation by inhibiting tyrosine phosphorylation and nuclear transcription of IL- 2, while TGF-beta inhibits only IL-2 receptor mediated proliferative signals.
