Down-regulation of the orphan nuclear receptor RORγt is essential for T lymphocyte maturation
Down-regulation of the orphan nuclear receptor RORγt is essential for T lymphocyte maturation
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DOI：
10.4049/jimmunol.164.11.5668
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发表时间：
2000-06-01
影响因子：
4.4
通讯作者：
Bevan, MJ
中科院分区：
文献类型：
--
作者：
He, YW;Beers, C;Bevan, MJ
胸腺细胞发育是一个受到严格调控的过程。 CD4(+)CD8(+)双阳性(DP)未成熟胸腺细胞表现出与成熟T细胞不同的表型特征；它们仅表达成熟 T 细胞表面 TCR 的 10%，并且不会响应刺激而增殖和产生 IL-2。在本报告中，我们表明成熟 T 细胞中孤儿核受体 ROR gamma t 的转基因表达下调了其表面 TCR 表达。 ROR gamma t转基因抑制成熟T细胞产生IL-2，这种抑制可能部分归因于ROR gamma t对c-Rel转录的抑制作用，此外，ROR gamma t的异位表达抑制成熟和未成熟T细胞的增殖。这些结果，连同其在 DP 胸腺细胞中的主要表达，表明 ROR gamma t 控制 DP 胸腺细胞的这些独特表型特征。我们的数据表明，胸腺细胞中 ROR gamma t 表达的下调对其成熟至关重要。
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 tells 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.