Single-cell profiling identifies T cell subsets associated with control of tuberculosis dissemination

To identify T cell subsets associated with control of tuberculosis, single-cell transcriptome and T cell receptor sequencing were performed on total T cells from patients with tuberculosis and healthy controls. Fourteen distinct subsets of T cells were identified by unbiased UMAP clustering. A GZMK-expressing CD8+ cytotoxic T cell cluster and a SOX4-expressing CD4+ central memory T cell cluster were depleted, while a MKI67-expressing proliferating CD3+ T cell cluster was expanded in patients with tuberculosis compared with healthy controls. The ratio of Granzyme K-expressing CD8+CD161−Ki-67− and CD8+Ki-67+ T cell subsets was significantly reduced and inversely correlated with the extent of TB lesions in patients with TB. In contrast, ratio of Granzyme B-expressing CD8+Ki-67+ and CD4+CD161+Ki-67− T cells and Granzyme A-expressing CD4+CD161+Ki-67− T cells were correlated with the extent of TB lesions. It is concluded that granzyme K-expressing CD8+ T cell subsets might contribute to protection against tuberculosis dissemination.