![]() Our ability to manage TB as a threat to global health is compromised by deficient elucidation of the immune response that influences the outcomes of Mycobacterium tuberculosis (Mtb) infection ( Jeyanathan et al., 2018 Tezera et al., 2020). Since 2007, tuberculosis (TB) has been the leading infectious disease cause of global deaths with 1.4 million deaths reported in 2019 ( Furin et al., 2019 World Health Organization, 2020). Furthermore, we identified a new subset of polyfunctional CD4 + T cells with CD1-restricted, T H1, and cytotoxic characteristics, and this subset might provide protective immunity against Mtb. A significant increase in clonality was observed in TCR repertoires in CD4 + T cells, but not in CD8 + T cells, although both enriched CD4 + and CD8 + T cells showed T H1 and cytotoxic signatures. Altered hydrophobicity was demonstrated in CDR3 in CD8 + T cells and a significant imbalance in the TCR usage pattern of T cells with preferential expression of TRBV4-1 in TPE. Compared with controls, no differences in length and profile of length distribution were observed in complementarity determining region 3 (CDR3) in both CD4 + and CD8 + T cells in TPE. By combining single-cell TCR sequencing (sc-TCR seq) with single-cell RNA sequencing (sc-RNA seq) and flow cytometry to characterize T cells in tuberculous pleural effusions (TPEs), we identified 41,718 CD3 + T cells in TPEs and paired blood samples, including 30,515 CD4 + T cells and 11,203 CD8 + T cells. The characteristics of TCR sequences and distinctive signatures of T cell subsets in tuberculous patients are still unclear. Characterization of T cell receptor (TCR) repertoires is essential for understanding the mechanisms of Mycobacterium tuberculosis (Mtb) infection involving T cell adaptive immunity.
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