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bioRxiv · 10.64898/2026.06.15.732401

NKG2C+CD27- Defines Human CD8+ Regulatory T Cells

Li, X.·Mistri, S. K.·Cao, T.·Krishnan, R. K.·Hemberg, M.·Weiner, H. L.·Hu, D.
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Abstract

Here we identify NKG2C+CD27- as a novel surface marker unifying multiple previously reported CD8+ regulatory T cell (Treg) populations. This population displays high clonality and divides into CD226- (Treg1) and CD226+ (Treg2) subsets, with Treg2 exhibiting stronger suppressive activities. Up to 35% of CD8+ TEMRA cells are Tregs, whereas approximately 85% of CD8+ Tregs are TEMRA cells, which increase with aging. These findings establish a unified and novel cell surface marker for CD8+ Tregs and their subsets, which resolves prior heterogeneity in the field, and show that CD8+ TEMRA cells are a heterogeneous population that includes T cells with regulatory function. Our findings provide a critical framework for the isolation and in-depth functional characterization of CD8+ Tregs in health, aging, and disease.

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Li, X., Mistri, S. K., Cao, T., Krishnan, R. K., Hemberg, M., Weiner, H. L., Hu, D.. 2026-06-17. NKG2C+CD27- Defines Human CD8+ Regulatory T Cells. https://doi.org/10.64898/2026.06.15.732401

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