{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T14:45:29Z","timestamp":1761489929510,"version":"3.38.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>HIV-infected persons are at greater risk of developing tuberculosis (TB) even before profound CD4 loss occurs, suggesting that HIV alters CD4+ T cell functions capable of containing bacterial replication. An effective immune response to Mycobacterium tuberculosis most likely relies on the development of a balanced CD4 response, in which distinct CD4+ Th subsets act in synergy to control the infection. To define the diversity of M. tuberculosis\u2013specific CD4+ Th subsets and determine whether HIV infection impacts such responses, the expression of lineage-defining transcription factors T-bet, Gata3, ROR\u03b3t, and Foxp3 was measured in M. tuberculosis\u2013specific CD4+ T cells in HIV-uninfected (n = 20) and HIV-infected individuals (n = 20) with latent TB infection. Our results show that, upon 5-d restimulation in vitro, M. tuberculosis\u2013specific CD4+ T cells from healthy individuals have the ability to exhibit a broad spectrum of Th subsets, defined by specific patterns of transcription factor coexpression. These transcription factor profiles were skewed in HIV-infected individuals where the proportion of T-bethighFoxp3+ \u00a0M. tuberculosis\u2013specific CD4+ T cells was significantly decreased (p = 0.002) compared with HIV-uninfected individuals, a change that correlated inversely with HIV viral load (p = 0.0007) and plasma TNF-\u03b1 (p = 0.027). Our data demonstrate an important balance in Th subset diversity defined by lineage-defining transcription factor coexpression profiles that is disrupted by HIV infection and suggest a role for HIV in impairing TB immunity by altering the equilibrium of M. tuberculosis\u2013specific CD4+ Th subsets.<\/jats:p>","DOI":"10.4049\/jimmunol.1502094","type":"journal-article","created":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T04:04:37Z","timestamp":1456805077000},"page":"3006-3018","source":"Crossref","is-referenced-by-count":23,"title":["HIV Skews the Lineage-Defining Transcriptional Profile of <i>Mycobacterium tuberculosis<\/i>\u2013Specific CD4+ T Cells"],"prefix":"10.1093","volume":"196","author":[{"given":"Catherine","family":"Riou","sequence":"first","affiliation":[{"name":"Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town , 7925, Cape Town ,","place":["South Africa"]},{"name":"Institute of Infectious Disease and Molecular Medicine, University of Cape Town , 7925, Cape Town ,","place":["South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Strickland","sequence":"additional","affiliation":[{"name":"Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town , 7925, Cape Town ,","place":["South Africa"]},{"name":"Institute of Infectious Disease and Molecular Medicine, University of Cape Town , 7925, Cape Town ,","place":["South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9003-222X","authenticated-orcid":false,"given":"Andreia P","family":"Soares","sequence":"additional","affiliation":[{"name":"Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town , 7925, Cape Town ,","place":["South Africa"]},{"name":"Institute of Infectious Disease and Molecular Medicine, University of Cape Town , 7925, Cape Town ,","place":["South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9833-3169","authenticated-orcid":false,"given":"Bj\u00f6rn","family":"Corleis","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard , Cambridge, MA 02139"},{"name":"Division of Infectious Diseases, Massachusetts General Hospital , Boston, MA 02139"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8521-8735","authenticated-orcid":false,"given":"Douglas S","family":"Kwon","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard , Cambridge, MA 02139"},{"name":"Division of Infectious Diseases, Massachusetts General Hospital , Boston, MA 02139"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E John","family":"Wherry","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute for Immunology, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2753-1800","authenticated-orcid":false,"given":"Robert J","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, University of Cape Town , 7925, Cape Town ,","place":["South Africa"]},{"name":"Department of Medicine, Imperial College London , London W21 PG ,","place":["United Kingdom"]},{"name":"Francis Crick Institute Mill Hill Laboratory , London NW7 1AA ,","place":["United Kingdom"]},{"name":"Clinical Infectious Diseases Research Initiative, University of Cape Town , 7925, Cape Town ,","place":["South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy A","family":"Burgers","sequence":"additional","affiliation":[{"name":"Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town , 7925, Cape Town ,","place":["South Africa"]},{"name":"Institute of Infectious Disease and Molecular Medicine, University of Cape Town , 7925, Cape Town ,","place":["South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,4,1]]},"reference":[{"key":"2025030702150949100_r1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nri3259","article-title":"The immunological life cycle of tuberculosis","volume":"12","author":"Ernst","year":"2012","journal-title":"Nat. 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