Department of Microbiology and Physiological Systems
Bacterial Infections and Mycoses | Hemic and Immune Systems | Immunity | Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Microbiology
Unconventional T cells that recognize mycobacterial antigens are of great interest as potential vaccine targets against tuberculosis (TB). This includes donor-unrestricted T cells (DURTs), such as mucosa-associated invariant T cells (MAITs), CD1-restricted T cells, and gammadelta T cells. We exploited the distinctive nature of DURTs and gammadelta T cell receptors (TCRs) to investigate the involvement of these T cells during TB in the human lung by global TCR sequencing. Making use of surgical lung resections, we investigated the distribution, frequency, and characteristics of TCRs in lung tissue and matched blood from individuals infected with TB. Despite depletion of MAITs and certain CD1-restricted T cells from the blood, we found that the DURT repertoire was well preserved in the lungs, irrespective of disease status or HIV coinfection. The TCRdelta repertoire, in contrast, was highly skewed in the lungs, where it was dominated by Vdelta1 and distinguished by highly localized clonal expansions, consistent with the nonrecirculating lung-resident gammadelta T cell population. These data show that repertoire sequencing is a powerful tool for tracking T cell subsets during disease.
Adaptive immunity, Immunology, Infectious disease, T-cell receptor, Tuberculosis
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Copyright: © 2019, Ogongo et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
DOI of Published Version
J Clin Invest. 2019 Nov 25. pii: 130711. doi: 10.1172/JCI130711. [Epub ahead of print] Link to article on publisher's site
The Journal of clinical investigation
Ogongo P, Steyn AJ, Karim F, Dullabh KJ, Awala I, Madansein R, Leslie A, Behar SM. (2019). Differential skewing of donor-unrestricted and gammadelta T cell repertoires in tuberculosis-infected human lungs. Open Access Publications by UMass Chan Authors. https://doi.org/10.1172/JCI130711. Retrieved from https://escholarship.umassmed.edu/oapubs/4040
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.