Etzensperger Ruth, Kadakia Tejas, Tai Xuguang, Alag Amala, Guinter Terry I, Egawa Takeshi, Erman Batu, Singer Alfred
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Nat Immunol. 2017 Nov;18(11):1218-1227. doi: 10.1038/ni.3847. Epub 2017 Sep 25.
T cell antigen receptor (TCR) signaling in the thymus initiates positive selection, but the CD8-lineage fate is thought to be induced by cytokines after TCR signaling has ceased, although this remains controversial and unproven. We have identified four cytokines (IL-6, IFN-γ, TSLP and TGF-β) that did not signal via the common γ-chain (γ) receptor but that, like IL-7 and IL-15, induced expression of the lineage-specifying transcription factor Runx3d and signaled the generation of CD8 T cells. Elimination of in vivo signaling by all six of these 'lineage-specifying cytokines' during positive selection eliminated Runx3d expression and completely abolished the generation of CD8 single-positive thymocytes. Thus, this study proves that signaling during positive selection by lineage-specifying cytokines is responsible for all CD8-lineage-fate 'decisions' in the thymus.
胸腺中的T细胞抗原受体（TCR）信号传导启动阳性选择，但是CD8谱系命运被认为是在TCR信号传导停止后由细胞因子诱导产生的，尽管这一点仍存在争议且未经证实。我们已经鉴定出四种不通过共同γ链（γ）受体发出信号的细胞因子（IL-6、IFN-γ、TSLP和TGF-β），但它们与IL-7和IL-15一样，可诱导谱系特异性转录因子Runx3d的表达，并发出CD8 T细胞生成的信号。在阳性选择过程中消除所有这六种“谱系特异性细胞因子”的体内信号传导，会消除Runx3d的表达，并完全消除CD8单阳性胸腺细胞的生成。因此，本研究证明，在阳性选择过程中由谱系特异性细胞因子进行的信号传导决定了胸腺中所有CD8谱系命运的“决策”。
