Abstract
Abstract In mice, two T-box transcription factors, T-bet and Eomes, drive the differentiation of CD8 T-cell lineages; however, little is known regarding their role in human CD8 T-cell differentiation. Here, we characterized T-bet and Eomes expression and localization within human CD8 memory T-cell populations. We find T-bet and Eomes are broadly expressed in human memory CD8 T cells, with increasing levels of T-bet and Eomes strongly correlating with differentiation from central memory to effector memory and effector subpopulations. Interestingly, T-bet levels directly correlate to subcellular localization, with a higher propensity for nuclear expression of T-bet within T-bethi cells and predominately cytoplasmic expression in T-betlo cells. In contrast, Eomes appears to be localized solely to the nucleus. In murine CD8 T cells, T-bet can be nuclear, cytoplasmic, or both; however, Eomes is detectable in both compartments suggesting differential regulation compared to humans. Additionally, in humans, Eomes tightly correlated with nuclear T-bet suggesting T-bet localization might impact Eomes expression. Together, our data provide a novel mechanism for CD8 T-cell differentiation in humans and mice based on subcellular localization of T-bet, and reveal the likely presence of previously unknown regulation mechanisms for these critical lineage defining transcription factors.
Published Version
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