Single-cell profiling identifies T cell subsets associated with control of tuberculosis dissemination
Jing Jiang, Zhihong Cao, Xiao Li, Jinwen Su, Jinhe Wang, Jianqin Liang, Bingfen Yang, Yanhua Liu, Fei Zhai, Ruo Wang, Xiaoxing Cheng
Abstract
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.