NKG2C + CD27 - Defines Human CD8 + Regulatory T Cells.

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 + T EMRA cells are Tregs, whereas approximately 85% of CD8 + Tregs are T EMRA 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 + T EMRA 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.