Transcriptional profile of Mycobacterium tuberculosis peptide-specific T cells in pulmonary granulomas

The function of Mycobacterium tuberculosis peptide-specific T cells in granulomas is incompletely understood. Here we profiled rhesus macaque and human Mtb-specific T cells by performing single cell RNA sequencing on granuloma cells stimulated with Mtb peptide pools. Mtb-specific T cells express pro-inflammatory cytokines, chemokines, TNF superfamily molecules, SLAM family molecules, semaphorins, growth factors, proteases and collagen. Peptide recognition by Mtb-specific T cells also drives expression of FLT3LG, LTA and XCL1 in bystander and unconventional CD8 T cells. Granuloma T cells express transcripts encoding multiple cytotoxic molecules, while peptide-specific T cells primarily express granzyme B. 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.