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).