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Accumulating evidence suggests that CD4+ T cells producing IL-22, a distinct subset termed \u201cTh22\u201d cells, may contribute to protective immunity to TB. Thus, we characterized Mycobacterium tuberculosis\u2013specific Th22 (and Th1 and Th17) cells in 72 people with latent TB infection or TB disease, with and without HIV-1 infection. We investigated the functional properties (IFN-\u03b3, IL-22, and IL-17 production), memory differentiation (CD45RA, CD27, and CCR7), and activation profile (HLA-DR) of M. tuberculosis\u2013specific CD4+ T cells. In HIV-uninfected individuals with latent TB infection, we detected abundant circulating IFN-\u03b3\u2013producing CD4+ T cells (median, 0.93%) and IL-22\u2013producing CD4+ T cells (median, 0.46%) in response to M. tuberculosis. The frequency of IL-17\u2013producing CD4+ T cells was much lower, at a median of 0.06%. Consistent with previous studies, IL-22 was produced by a distinct subset of CD4+ T cells and not coexpressed with IL-17. M. tuberculosis\u2013specific IL-22 responses were markedly reduced (median, 0.08%) in individuals with TB disease and HIV coinfection compared with IFN-\u03b3 responses. M. tuberculosis\u2013specific Th22 cells exhibited a distinct memory and activation phenotype compared with Th1 and Th17 cells. Furthermore, M. tuberculosis\u2013specific IL-22 was produced by conventional CD4+ T cells that required TCR engagement. In conclusion, we confirm that Th22 cells are a component of the human immune response to TB. Depletion of M. tuberculosis\u2013specific Th22 cells during HIV coinfection may contribute to increased risk of TB disease.<\/jats:p>","DOI":"10.4049\/jimmunol.2200140","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T11:15:19Z","timestamp":1657797319000},"page":"446-455","source":"Crossref","is-referenced-by-count":8,"title":["Characterization of\n                    <i>Mycobacterium tuberculosis<\/i>\n                    \u2013Specific Th22 Cells and the Effect of Tuberculosis Disease and HIV Coinfection"],"prefix":"10.1093","volume":"209","author":[{"given":"Mohau S","family":"Makatsa","sequence":"first","affiliation":[{"name":"Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town , Cape Town,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1332-2167","authenticated-orcid":false,"given":"F Millicent A","family":"Omondi","sequence":"additional","affiliation":[{"name":"Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town , Cape Town,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8471-163X","authenticated-orcid":false,"given":"Rubina","family":"Bunjun","sequence":"additional","affiliation":[{"name":"Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town , Cape Town,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town , Cape Town,","place":["South Africa"]},{"name":"Institute of Infectious Disease and Molecular Medicine, University of Cape Town , Cape Town,","place":["South Africa"]},{"name":"Department of Medicine, Imperial College London , London,","place":["U.K."]},{"name":"Francis Crick Institute Mill Hill laboratory , London,","place":["U.K."]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9679-0745","authenticated-orcid":false,"given":"Catherine","family":"Riou","sequence":"additional","affiliation":[{"name":"Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town , Cape Town,","place":["South Africa"]},{"name":"Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town , Cape Town,","place":["South Africa"]},{"name":"Institute of Infectious Disease and Molecular Medicine, University of Cape Town , Cape Town,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3396-9398","authenticated-orcid":false,"given":"Wendy A","family":"Burgers","sequence":"additional","affiliation":[{"name":"Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town , Cape Town,","place":["South Africa"]},{"name":"Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town , Cape Town,","place":["South Africa"]},{"name":"Institute of Infectious Disease and Molecular Medicine, University of Cape Town , Cape Town,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,1]]},"reference":[{"key":"2025021008233286700_r1","article-title":"Global tuberculosis report 2019","author":"World Health Organization","year":"2019"},{"key":"2025021008233286700_r2","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1146\/annurev-immunol-032712-095939","article-title":"The immune response in tuberculosis","volume":"31","author":"O\u2019Garra","year":"2013","journal-title":"Annu. Rev. Immunol."},{"key":"2025021008233286700_r3","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/S0140-6736(95)92348-9","article-title":"Variation in protection by BCG: implications of and for heterologous immunity","volume":"346","author":"Fine","year":"1995","journal-title":"Lancet"},{"key":"2025021008233286700_r4","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/S0140-6736(06)68507-3","article-title":"Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness","volume":"367","author":"Trunz","year":"2006","journal-title":"Lancet"},{"key":"2025021008233286700_r5","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1056\/NEJMoa1909953","article-title":"Final analysis of a trial of M72\/AS01E vaccine to prevent tuberculosis","volume":"381","author":"Tait","year":"2019","journal-title":"N. Engl. J. 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