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dc.contributor.authorOgongo, Paul
dc.contributor.authorTezera, Liku B.
dc.contributor.authorArdain, Amanda
dc.contributor.authorNhamoyebonde, Shepherd
dc.contributor.authorRamsuran, Duran
dc.contributor.authorSingh, Alveera
dc.contributor.authorNg'oepe, Abigail
dc.contributor.authorKarim, Farina
dc.contributor.authorNaidoo, Taryn
dc.contributor.authorKhan, Khadija
dc.contributor.authorDullabh, Kaylesh J.
dc.contributor.authorFehlings, Michael
dc.contributor.authorLee, Boon Heng.
dc.contributor.authorNardin, Alessandra
dc.contributor.authorLindestam Arlehamn, Cecilia S.
dc.contributor.authorSette, Alessandro
dc.contributor.authorBehar, Samuel M.
dc.contributor.authorSteyn, Adrie Jc.
dc.contributor.authorMadansein, Rajhmun
dc.contributor.authorKloverpris, Henrik N.
dc.contributor.authorElkington, Paul T.
dc.contributor.authorLeslie, Alasdair
dc.date2022-08-11T08:10:00.000
dc.date.accessioned2022-08-23T16:51:52Z
dc.date.available2022-08-23T16:51:52Z
dc.date.issued2021-05-17
dc.date.submitted2021-09-24
dc.identifier.citation<p>Ogongo P, Tezera LB, Ardain A, Nhamoyebonde S, Ramsuran D, Singh A, Ng'oepe A, Karim F, Naidoo T, Khan K, Dullabh KJ, Fehlings M, Lee BH, Nardin A, Lindestam Arlehamn CS, Sette A, Behar SM, Steyn AJ, Madansein R, Kløverpris HN, Elkington PT, Leslie A. Tissue-resident-like CD4+ T cells secreting IL-17 control Mycobacterium tuberculosis in the human lung. J Clin Invest. 2021 May 17;131(10):e142014. doi: 10.1172/JCI142014. PMID: 33848273; PMCID: PMC8121523. <a href="https://doi.org/10.1172/JCI142014">Link to article on publisher's site</a></p>
dc.identifier.issn0021-9738 (Linking)
dc.identifier.doi10.1172/JCI142014
dc.identifier.pmid33848273
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41940
dc.description.abstractT cell immunity is essential for the control of tuberculosis (TB), an important disease of the lung, and is generally studied in humans using peripheral blood cells. Mounting evidence, however, indicates that tissue-resident memory T cells (Trms) are superior at controlling many pathogens, including Mycobacterium tuberculosis (M. tuberculosis), and can be quite different from those in circulation. Using freshly resected lung tissue, from individuals with active or previous TB, we identified distinct CD4+ and CD8+ Trm-like clusters within TB-diseased lung tissue that were functional and enriched for IL-17-producing cells. M. tuberculosis-specific CD4+ T cells producing TNF-alpha, IL-2, and IL-17 were highly expanded in the lung compared with matched blood samples, in which IL-17+ cells were largely absent. Strikingly, the frequency of M. tuberculosis-specific lung T cells making IL-17, but not other cytokines, inversely correlated with the plasma IL-1beta levels, suggesting a potential link with disease severity. Using a human granuloma model, we showed the addition of either exogenous IL-17 or IL-2 enhanced immune control of M. tuberculosis and was associated with increased NO production. Taken together, these data support an important role for M. tuberculosis-specific Trm-like, IL-17-producing cells in the immune control of M. tuberculosis in the human lung.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=33848273&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/pmc8121523/
dc.rights© 2021 Ogongo et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectBacterial infections
dc.subjectImmunology
dc.subjectInfectious disease
dc.subjectT cells
dc.subjectBacteria
dc.subjectBacterial Infections and Mycoses
dc.subjectHemic and Immune Systems
dc.subjectImmunology of Infectious Disease
dc.subjectImmunopathology
dc.subjectInfectious Disease
dc.titleTissue-resident-like CD4+ T cells secreting IL-17 control Mycobacterium tuberculosis in the human lung
dc.typeJournal Article
dc.source.journaltitleThe Journal of clinical investigation
dc.source.volume131
dc.source.issue10
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5777&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4744
dc.identifier.contextkey25103806
refterms.dateFOA2022-08-23T16:51:52Z
html.description.abstract<p>T cell immunity is essential for the control of tuberculosis (TB), an important disease of the lung, and is generally studied in humans using peripheral blood cells. Mounting evidence, however, indicates that tissue-resident memory T cells (Trms) are superior at controlling many pathogens, including Mycobacterium tuberculosis (M. tuberculosis), and can be quite different from those in circulation. Using freshly resected lung tissue, from individuals with active or previous TB, we identified distinct CD4+ and CD8+ Trm-like clusters within TB-diseased lung tissue that were functional and enriched for IL-17-producing cells. M. tuberculosis-specific CD4+ T cells producing TNF-alpha, IL-2, and IL-17 were highly expanded in the lung compared with matched blood samples, in which IL-17+ cells were largely absent. Strikingly, the frequency of M. tuberculosis-specific lung T cells making IL-17, but not other cytokines, inversely correlated with the plasma IL-1beta levels, suggesting a potential link with disease severity. Using a human granuloma model, we showed the addition of either exogenous IL-17 or IL-2 enhanced immune control of M. tuberculosis and was associated with increased NO production. Taken together, these data support an important role for M. tuberculosis-specific Trm-like, IL-17-producing cells in the immune control of M. tuberculosis in the human lung.</p>
dc.identifier.submissionpathoapubs/4744
dc.contributor.departmentDepartment of Microbiology and Physiological Systems
dc.source.pagese142014


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© 2021 Ogongo et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's license is described as © 2021 Ogongo et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.