Eomes expression reports the progressive differentiation of IFN-gamma-producing Th1-like gamma delta Tcells

摘要

The transcription factor Eomesodermin (Eomes) plays a crucial role in regulating cytotoxic function, development gamma delta and survival of immune cells. Tcells can express Eomes, but its contribution to their differentiation is unknown. Using Eomes-IRES-GFP mice, we show that Eomes(+) gamma delta T cells are unequally distributed among organs, with the highest proportion in spleen. While the majority of Eomes(+) gamma delta T cells expressed V gamma 1(+) and V gamma 4(+) TCRs, Eomes was absent in V gamma 5(+), V gamma 6(+), and V gamma 7(+) subsets. Moreover, Eomes was co-expressed in gamma delta Tcells with Th1 lineage-related factors such as CD27, T-bet, and Ly6C, but not with Th17 lineage-related genes. Eomes(+) and Eomes T-cell populations showed distinct gene expression profiles, with an increase of cytotoxic-related genes in Eomes(+) gamma delta Tcells. Furthermore, Eomes could be induced in peripheral gamma delta T cells by IL-12 and IL-4, and Eomes(+) gamma delta Tcells presented a higher proliferation rate and IFN- production when stimulated in vitro with IL-12 and IL-18. However, gamma delta Tcells with very high Eomes levels displayed an exhausted phenotype with high levels of PD-1, and were less capable of IFN-gamma production. Together, this study highlights Eomes as a marker for the differentiation of Th1-like effector gamma delta Tcells.