Eomes expression reports the progressive differentiation of IFN‐γ‐producing Th1‐like γδ T cells

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.