Institute of Immunology, Hannover Medical School, Hannover, Germany.
CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil.
Eur J Immunol. 2017 Jun;47(6):970-981. doi: 10.1002/eji.201646753. Epub 2017 Apr 24.
The transcription factor Eomesodermin (Eomes) plays a crucial role in regulating cytotoxic function, development, and survival of immune cells. γδ T cells can express Eomes, but its contribution to their differentiation is unknown. Using Eomes-IRES-GFP mice, we show that Eomes γδ T cells are unequally distributed among organs, with the highest proportion in spleen. While the majority of Eomes γδ T cells expressed Vγ1 and Vγ4 TCRs, Eomes was absent in Vγ5 , Vγ6 , and Vγ7 subsets. Moreover, Eomes was co-expressed in γδ T cells with Th1 lineage-related factors such as CD27, T-bet, and Ly6C, but not with Th17 lineage-related genes. Eomes and Eomes γδ T-cell populations showed distinct gene expression profiles, with an increase of cytotoxic-related genes in Eomes γδ T cells. Furthermore, Eomes could be induced in peripheral γδ T cells by IL-12 and IL-4, and Eomes γδ T cells presented a higher proliferation rate and IFN-γ production when stimulated in vitro with IL-12 and IL-18. However, γδ T cells with very high Eomes levels displayed an exhausted phenotype with high levels of PD-1, and were less capable of IFN-γ production. Together, this study highlights Eomes as a marker for the differentiation of Th1-like effector γδ T cells.
转录因子 Eomesodermin (Eomes) 在调节免疫细胞的细胞毒性功能、发育和存活方面发挥着关键作用。γδ T 细胞可以表达 Eomes，但它对其分化的贡献尚不清楚。使用 Eomes-IRES-GFP 小鼠，我们表明 Eomes γδ T 细胞在器官中的分布不均，脾脏中比例最高。虽然大多数 Eomes γδ T 细胞表达 Vγ1 和 Vγ4 TCR，但 Vγ5、Vγ6 和 Vγ7 亚群中不存在 Eomes。此外，Eomes 与 Th1 谱系相关因子（如 CD27、T-bet 和 Ly6C）共同表达于 γδ T 细胞中，但与 Th17 谱系相关基因无关。Eomes 和 Eomes γδ T 细胞群体表现出不同的基因表达谱，Eomes γδ T 细胞中细胞毒性相关基因增加。此外，IL-12 和 IL-4 可诱导外周 γδ T 细胞中 Eomes 的表达，Eomes γδ T 细胞在体外受到 IL-12 和 IL-18 的刺激时，增殖率和 IFN-γ 产生增加。然而，具有非常高 Eomes 水平的 γδ T 细胞表现出 PD-1 水平高的耗竭表型，并且 IFN-γ 产生能力降低。总之，这项研究强调了 Eomes 作为 Th1 样效应 γδ T 细胞分化的标志物。
