Precursors of exhausted T cells are pre-emptively formed in acute infection

Abstract T cell exhaustion limits effector T cell function in chronic infection and tumours 1,2 . The development of these hypofunctional T cells and of their precursors was considered to require stimulatory conditions that are met only after persistent exposure to antigen and inflammation. Here we show, however, that similar T cell populations exist in the early phase of acute infections 1,2 . At that stage, the early developing TCF1 + precursor population exhibits an unexpected diversity; it includes precursors of normal memory T cells, but also cells with phenotypic, gene-expression and epigenetic profiles that resemble those of precursors of exhausted T cells found in chronic infections. We show that high…