CD4 and infection: Three major points emerged from our study: 1) The acute response to M.tb-infection in humans was associated with highly activated M.tb-specific CD4 T cells that are moderately differentiated; 2) During remote infection M.tb-specific T cells were not activated but showed a phenotype consistent with long-term antigen exposure without evidence of exhaustion; 3) Among all the differences in M.tb-specific T cell phenotype and functions, HLA-DR expression had the highest diagnostic performance to distinguish between recent and remote infection.