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t Is Essential for T Lymphocyte Maturation1
Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195
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
t in mature T cells down-regulates their surface TCR
expression. The RORt transgene inhibits IL-2 production by mature T
cells, and this inhibition may be partially due to the inhibitory
effect of RORt on c-Rel transcription. Furthermore, ectopic
expression of RORt inhibits the proliferation of mature and immature
T cells. These results, together with its predominant expression in DP
thymocytes, suggest that RORt controls these distinct phenotypic
features of DP thymocytes. Our data suggest that down-regulation of
RORt expression in thymocytes is essential for their
maturation.
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