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.
Duke Scholars
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- fas Receptor
- Up-Regulation
- Transgenes
- Thymus Gland
- T-Lymphocyte Subsets
- Receptors, Thyroid Hormone
- Receptors, Retinoic Acid
- Receptors, Cytoplasmic and Nuclear
- Receptors, Antigen, T-Cell
- Proto-Oncogene Proteins c-rel
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- fas Receptor
- Up-Regulation
- Transgenes
- Thymus Gland
- T-Lymphocyte Subsets
- Receptors, Thyroid Hormone
- Receptors, Retinoic Acid
- Receptors, Cytoplasmic and Nuclear
- Receptors, Antigen, T-Cell
- Proto-Oncogene Proteins c-rel