Development of promyelocytic leukemia zinc finger-expressing innate CD4 T cells requires stronger T-cell receptor signals than conventional CD4 T cells.
Development of promyelocytic leukemia zinc finger-expressing innate CD4 T cells requires stronger T-cell receptor signals than conventional CD4 T cells.
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早幼粒细胞白血病表达锌指的先天性 CD4 T 细胞的发育需要比传统 CD4 T 细胞更强的 T 细胞受体信号。
DOI：
10.1073/pnas.1207528109
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发表时间：
2012
影响因子：
11.1
通讯作者：
Ch
中科院分区：
文献类型：
--
作者：
Qiao,Yu;Zhu,Lingqiao;Sofi,Hanief;Lapinski,PhilipE;Horai,Reiko;Mueller,Kristen;Stritesky,GrettaL;He,Xi;Teh,Hung-Sia;Wiest,DavidL;Kappes,DietmarJ;King,PhilipD;Hogquist,KristinA;Schwartzberg,PamelaL;Sant'Angelo,DerekB;Ch
表达MHC II类的胸腺细胞和胸腺上皮细胞可以介导CD 4 T细胞选择，分别产生功能不同的胸腺细胞选择的CD 4（T-CD 4）和上皮选择的CD 4（E-CD 4）T细胞。然而，关于T细胞受体（TCR）信号传导如何影响这两个CD 4 T细胞亚群的发育知之甚少。为了研究T-CD 4 T细胞发育的TCR信号传导，我们使用了Nur 77的GFP报告系统，其中GFP强度与TCR信号传导强度直接相关。T-CD 4 T细胞比E-CD 4 T细胞表达更高水平的GFP，表明在选择期间T-CD 4 T细胞比E-CD 4 T细胞接受更强的TCR信号传导。Ras GTP酶激活蛋白的消除增强了E-CD 4，但降低了T-CD 4 T细胞选择效率，表明向阴性选择的转变。相反，由于TCR信号传导不足而导致不良E-CD 4 T细胞选择的IL-2诱导型T细胞激酶的缺乏改善了T-CD 4 T细胞的产生，这与从阴性选择中的拯救一致。T-CD 4 T细胞发育过程中强TCR信号传导与转录因子早幼粒细胞白血病锌指蛋白的表达相关然而，尽管信号强度的调节影响了阳性和阴性选择期间T-CD 4 T细胞发育的效率，但信号强度对于T-CD 4 T细胞的效应子功能并不那么重要。这些发现表明，先天性T-CD 4 T细胞，以及不变的自然杀伤T细胞和γδ T细胞，在其发育过程中接收强TCR信号，并且发育和效应功能的信号传导要求是不同的。
MHC class II-expressing thymocytes and thymic epithelial cells can mediate CD4 T-cell selection resulting in functionally distinct thymocyte-selected CD4 (T-CD4) and epithelial-selected CD4 (E-CD4) T cells, respectively. However, little is known about how T-cell receptor (TCR) signaling influences the development of these two CD4 T-cell subsets. To study TCR signaling for T-CD4 T-cell development, we used a GFP reporter system of Nur77 in which GFP intensity directly correlates with TCR signaling strength. T-CD4 T cells expressed higher levels of GFP than E-CD4 T cells, suggesting that T-CD4 T cells received stronger TCR signaling than E-CD4 T cells during selection. Elimination of Ras GTPase-activating protein enhanced E-CD4 but decreased T-CD4 T-cell selection efficiency, suggesting a shift to negative selection. Conversely, the absence of IL-2–inducible T-cell kinase that causes poor E-CD4 T-cell selection due to insufficient TCR signaling improved T-CD4 T-cell generation, consistent with rescue from negative selection. Strong TCR signaling during T-CD4 T-cell development correlates with the expression of the transcription factor promyelocytic leukemia zinc finger protein. However, although modulation of the signaling strength affected the efficiency of T-CD4 T-cell development during positive and negative selection, the signaling strength is not as important for the effector function of T-CD4 T cells. These findings indicate that innate T-CD4 T cells, together with invariant natural killer T cells and γδ T cells, receive strong TCR signals during their development and that signaling requirements for the development and the effector functions are distinct.