Multimodally profiling memory T cells from a tuberculosis cohort identifies cell state associations with demographics, environment and disease

Multimodal T cell profiling can enable more precise characterization of elusive states underlying disease. Here, we integrated single-cell RNA and surface protein data from 500,089 memory cells to define 31 259 individuals in a Peruvian tuberculosis (TB) progression cohort. At immune steady state >4 years after infection disease resolution, found that, accounting for significant effects age, sex, season genetic ancestry on composition, polyfunctional type 17 helper (TH17) cell–like effector was reduced abundance function who previously progressed Mycobacterium (M.tb) active TB These are capable responding M.tb peptides. Deconvoluting this state—uniquely identifiable with multimodal analysis—from public demonstrated that its depletion may precede persist beyond Our study demonstrates the power integrative relevant other traits. Raychaudhuri colleagues use high-dimensional analysis human They identify TH17–like cluster reactive peptides is people