Ligand-independent down-regulation of IFN-gamma receptor 1 following TCR engagement

Activated T lymphocytes modulate the level of many molecules on their cell surface, including cytokine receptors, This regulation of cytokine receptor expression affects the ability of T cells to respond to cytokines and thus influences the outcome of an immune response, The receptor for IFN-gamma, a proinflammatory cytokine, consists of two copies of a ligand binding chai n (IFN-gamma R1) as well as two copies of a second chain (IFN-gamma R2) req uired for signal transduction, The expression of IFN-gamma R2 is down-regul ated at the mRNA level on CD4(+) T cells when they differentiate into the T h1, but not the Th2, phenotype, This down-regulation has been demonstrated to depend on the ligand, IFN-gamma, which is produced by Th1 but not Th2 T cells. The regulation of the cell-surface expression of IFN-gamma receptors during primary T cell activation has not been reported. Naive and differen tiated T lymphocytes express IFN-gamma R1 at the mRNA level and as a cell-s urface protein, In this study, we present evidence that cell-surface expres sion of IFN-gamma R1 is transiently down-regulated on the surface of naive CD4(+) T cells shortly after TCR engagement. Furthermore, this down-regulat ion is not mediated by the ligand, IFN-gamma, but results from TCR engageme nt and ran be inhibited by cyclosporin A.