Differential skewing of donor-unrestricted and gammadelta T cell repertoires in tuberculosis-infected human lungs
Authors
Ogongo, PaulSteyn, Adrie Jc.
Karim, Farina
Dullabh, Kaylesh J.
Awala, Ismael
Madansein, Rajhmun
Leslie, Alasdair
Behar, Samuel M.
UMass Chan Affiliations
Department of Microbiology and Physiological SystemsDocument Type
Journal ArticlePublication Date
2019-11-25Keywords
Adaptive immunityImmunology
Infectious disease
T-cell receptor
Tuberculosis
Bacterial Infections and Mycoses
Hemic and Immune Systems
Immunity
Immunology of Infectious Disease
Immunoprophylaxis and Therapy
Microbiology
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Show full item recordAbstract
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.Source
J Clin Invest. 2019 Nov 25. pii: 130711. doi: 10.1172/JCI130711. [Epub ahead of print] Link to article on publisher's site
DOI
10.1172/JCI130711Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41254PubMed ID
31763997Related Resources
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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.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1172/JCI130711
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Except where otherwise noted, this item's license is described as Copyright: © 2019, Ogongo et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.