Characterization of human CD4 + EOMES + GzmK + T-cell subsets unveils an uncoupling of suppressive functions from IL-10-producing capacities.

Human CD4 + EOMES + T cells are heterogeneous and contain Th1-cells, Tr1-cells, and CD4 + CTL. Tr1- cells and non-classical EOMES + Th1-cells displayed, respectively, anti- and pro-inflammatory cytokine profiles, but both expressed granzyme-K, produced IFN-γ, and suppressed T-cell proliferation. Diffusion map suggested a progressive CD4 + T-cell differentiation from naïve to cytotoxic cells and identified EOMES + Th1-cells as putative Tr1-cell precursors (pre-Tr1).