Genetic evidence supporting selection of the Vα14i NKT cell lineage from double-positive thymocyte precursors
Genetic evidence supporting selection of the Vα14i NKT cell lineage from double-positive thymocyte precursors
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DOI：
10.1016/j.immuni.2005.03.011
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发表时间：
2005-06-01
期刊：
影响因子：
32.4
通讯作者：
Littman, DR
中科院分区：
文献类型：
--
作者：
Egawa, T;Eberl, G;Littman, DR
不变Vα14i NKT(INKT)细胞是具有调节功能的T淋巴细胞的特化亚群。它们共同表达TCRα、β和自然杀伤细胞标记。它们通过其Vα14-Jα18不变的TCRα链与表达在双阳性(DP)胸腺细胞上的CD1d相互作用而分化。虽然它们的发育已经被证明是胸腺依赖的，但它们的发育途径还没有明确地建立起来。通过使用遗传分析，我们在这里表明，所有iNKT细胞都是从DP胸腺细胞池中挑选出来的。它们的发育完全依赖于RUNX1和ROR Gamma t，这两种转录因子影响常规T细胞的发育，但不是必需的。我们的结果表明，尽管尚未观察到CD1d结合的DP胸腺细胞，但这些细胞中的Vα14-Jα18重排是iNKT细胞发育所必需的。
Invariant V alpha 14i NKT (iNKT) cells are a specialized subset of T lymphocytes with regulatory functions. They coexpress TCR alpha beta and natural killer cell markers. They differentiate through interaction of their V alpha 14-J alpha 18 invariant TCR alpha chains with CD1d expressed on double-positive (DP) thymocytes. Although their development has been shown to be thymus dependent, their developmental pathway has not been definitively established. By using genetic analyses, we show here that all iNKT cells are selected from a pool of DP thymocytes. Their development is absolutely dependent on Runx1 and ROR gamma t, transcription factors that influence, but are not required for, development of conventional T cells. Our results indicate that even though CD1d binding DP thymocytes have yet to be observed, V alpha 14-J alpha 18 rearrangement in these cells is required for development of iNKT cells.