生物
CD8型
细胞毒性T细胞
谱系(遗传)
细胞生物学
T细胞受体
免疫学
转录因子
否定选择
T细胞
抗原
免疫系统
遗传学
体外
基因
基因组
作者
Ruth Etzensperger,Tejas Kadakia,Xuguang Tai,Amala Alag,Terry I. Guinter,Takeshi Egawa,Batu Erman,Alfred Singer
出处
期刊:Nature Immunology
[Springer Nature]
日期:2017-09-25
卷期号:18 (11): 1218-1227
被引量:28
摘要
T cells developing in the thymus are signaled during positive selection to differentiate into either CD4+ T cells or CD8+ T cells. Singer and colleagues show that CD8+-lineage specification is signaled exclusively by cytokines, including cytokines that do not signal via the γc receptor, and that these are the only signals in the thymus that upregulate the transcription factor Runx3d to direct specification to the CD8+ lineage. 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 (γc) 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.
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