Enrichment of CD4-CD8- cytotoxic Vδ1/3 T cells in pulmonary tuberculosis disease

Although gamma-delta (γδ) T cells have increasingly been suggested to contribute to the TB immune response, quantitative and qualitative differences in this immune cell compartment between healthy and diseased individuals are not well-characterized. In this study, we used single-cell RNA sequencing to provide a high-resolution characterization of CD4-CD8- γδ T cells in peripheral blood across healthy Mtb-(non-)sensitized and TB disease pre-/post-treatment cohorts.

We found an activated and cytotoxic gene signature in γδ T cells of TB disease compared to both healthy cohorts. Strikingly, these differences persisted through one year following TB disease diagnosis. These transcriptomic differences were largely mediated by an NK-like cytotoxic Vδ1 and Vδ3 subset that was enriched in TB disease.