Orchestration of an effective T lymphocyte response at infection sites is critical for protection against Mycobacterium tuberculosis (Mtb) infection. However, the local T cell immunity landscape in human tuberculosis is poorly defined. Tuberculous pleural effusion (TPE), caused by Mtb, is characterized by an influx of leukocytes to the pleural space, providing a platform suitable for delineating complex tissue responses to Mtb infection. Using single-cell transcriptomics and T cell receptor sequencing, we analyzed mononuclear cell populations in paired pleural fluid and peripheral blood of TPE patients. While all major cell clusters were present in both tissues, their relative proportions varied significantly by anatomic location. Lineage tracking analysis revealed subsets of CD8 and CD4 T cell populations with distinct effector functions specifically expanded at pleural sites. Granzyme K–expressing CD8 T cells were preferentially enriched and clonally expanded in pleural fluid from TPE, suggesting that they are involved in the pathogenesis of the disease. The findings collectively reveal the landscape of local T cell immunity in tuberculosis.
Single-cell immune profiling reveals functional diversity of T cells in tuberculous pleural effusion
Disclosures: The authors declare no competing interests exist.
- Award Id(s): 81871255,82100015,82072252,91942315
- Award Id(s): 2019B030301009
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Yi Cai, Yejun Wang, Chenyan Shi, Youchao Dai, Fuxiang Li, Yuzhong Xu, Peize Zhang, Fanhui Kong, Guofang Deng, Zhihua Wen, Qi Zhou, Boxi Chris Kang, Amit Singhal, Qianting Yang, Carl G. Feng, Xinchun Chen; Single-cell immune profiling reveals functional diversity of T cells in tuberculous pleural effusion. J Exp Med 7 March 2022; 219 (3): e20211777. doi: https://doi.org/10.1084/jem.20211777
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