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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.

2026-06-17 immunology
10.64898/2026.06.15.732401 bioRxiv
Show 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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