Down-regulation of the orphan nuclear receptor ROR gamma t is essential for T lymphocyte maturation.
Thymocyte development is a tightly regulated process. CD4+CD8+ double-positive (DP) immature thymocytes exhibit distinct phenotypic features from mature T cells; they express only 10% of surface TCR that are found on mature T cells and do not proliferate and produce IL-2 in response to stimulation. In this report we show that transgenic expression of the orphan nuclear receptor ROR gamma t in mature T cells down-regulates their surface TCR expression. The ROR gamma t transgene inhibits IL-2 production by mature T cells, and this inhibition may be partially due to the inhibitory effect of ROR gamma t on c-Rel transcription. Furthermore, ectopic expression of ROR gamma t inhibits the proliferation of mature and immature T cells. These results, together with its predominant expression in DP thymocytes, suggest that ROR gamma t controls these distinct phenotypic features of DP thymocytes. Our data suggest that down-regulation of ROR gamma t expression in thymocytes is essential for their maturation.[1]References
- Down-regulation of the orphan nuclear receptor ROR gamma t is essential for T lymphocyte maturation. He, Y.W., Beers, C., Deftos, M.L., Ojala, E.W., Forbush, K.A., Bevan, M.J. J. Immunol. (2000) [Pubmed]
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