支持从双阳性胸腺细胞前体中选择Valpha14i自然杀伤T细胞谱系的遗传学证据。

Genetic evidence supporting selection of the Valpha14i NKT cell lineage from double-positive thymocyte precursors.

作者信息

Egawa Takeshi, Eberl Gerard, Taniuchi Ichiro, Benlagha Kamel, Geissmann Frederic, Hennighausen Lothar, Bendelac Albert, Littman Dan R

机构信息

Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.

出版信息

Immunity. 2005 Jun;22(6):705-16. doi: 10.1016/j.immuni.2005.03.011.

DOI:10.1016/j.immuni.2005.03.011

PMID:15963785

Abstract

Invariant Valpha14i NKT (iNKT) cells are a specialized subset of T lymphocytes with regulatory functions. They coexpress TCRalphabeta and natural killer cell markers. They differentiate through interaction of their Valpha14-Jalpha18 invariant TCRalpha 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, Valpha14-Jalpha18 rearrangement in these cells is required for development of iNKT cells.

摘要

不变的Vα14i自然杀伤T细胞（iNKT细胞）是具有调节功能的T淋巴细胞的一个特殊亚群。它们共表达TCRαβ和自然杀伤细胞标志物。它们通过其Vα14-Jα18不变TCRα链与双阳性（DP）胸腺细胞上表达的CD1d相互作用而分化。尽管已表明它们的发育依赖胸腺，但其发育途径尚未明确确立。通过基因分析，我们在此表明所有iNKT细胞均从DP胸腺细胞池中被选择。它们的发育绝对依赖于Runx1和ROR(γ)t，这两种转录因子影响传统T细胞的发育，但并非传统T细胞发育所必需。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重排对于iNKT细胞的发育是必需的。