Mycobacterium tuberculosis peptide-specific T cells in pulmonary granulomas display broad effector functions

Mycobacterium tuberculosis (Mtb) peptide-specific T cell responses in granulomas are essential for host protection. Here we profiled macaque and human granuloma Mtb-specific T cells with single cell RNA sequencing after stimulation with peptide pools. Mtb peptide-specific T cells are primarily Th1^∗ cells and express pro-inflammatory cytokines, mutiple chemokines, TNF superfamily molecules, granzyme B and perforin, SLAM family molecules, semaphorins, growth factors, proteases, and collagen. Peptide recognition by Mtb-specific T cells also drives responses in bystander and unconventional T cells including expression of FLT3LG, LTA, and XCL1. In granulomas from a patient that underwent a pneumonectomy to remove tuberculosis-destroyed lung, we identify a population of peptide-specific T cells similar to macaque peptide-stimulated T cells. Thus, Mtb peptide-specific T cells may mediate protection against Mtb infection through the combined effects of many functions as well as the induction of bystander responses by neighboring T cells.