The role of orphan nuclear receptor in thymocyte differentiation and lymphoid organ development.

T lymphocytes differentiate in the thymus through several phenotypically distinct stages that are tightly regulated by multiple nuclear transcription factors. Immature CD4+CD8+ double positive (DP) thymocytes make up a majority of the population in the thymus, and exhibit several phenotypic features distinct from mature T cells. DP thymocytes express only about 10% of surface TCR that are found on mature T cells and do not proliferate and produce IL-2 in response to stimulation. Several critical events of T lymphocyte maturation such as TCRalpha gene recombination, positive and negative selection, and CD4/CD8 lineage commitment occur around the DP stage. Recent studies from our group and others on the orphan nuclear receptor RORgamma and its thymus-specific isoform RORgammat support a critical role for this nuclear receptor in the regulation of DP thymocyte function. In addition, RORgamma is required for the development of lymph nodes and Peyer's patches.