RORγt, a novel isoform of an orphan receptor, negatively regulates Fas ligand expression and IL-2 production in T cells

We have identified ROR gamma t, a novel, thymus-specific isoform of the orphan nuclear receptor ROR gamma that is expressed predominantly in CD4(+) CD8(+) double-positive thymocytes. Ectopic expression of ROR gamma t protects T cell hybridomas from activation-induced cell death by inhibiting the upregulation of Pas ligand. Following hybridoma stimulation, ROR gamma t also inhibits IL-2 production but does not affect the induction of Nur-77 and Egr-3 nor the upregulation of sing. Both the ligand-binding and DNA-binding domains of ROR gamma t are required for this effect. We propose that the role of ROR gamma t expression in immature thymocytes is to inhibit Pas ligand expression and cytokine secretion following engagement of their TCR during positive or negative selection.