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HIV-associated dysregulation of adaptive immunity by depletion of CD4 Th cells most likely contributes to loss of immune control of LTBI in HIV-infected individuals, although the precise mechanisms whereby HIV infection impedes successful T cell\u2013mediated control of M. tuberculosis have not been well defined. To further delineate mechanisms whereby HIV impairs protective immunity to M. tuberculosis, we evaluated the frequency, phenotype, and functional capacity of M. tuberculosis-specific CD4 T cells in HIV-infected and HIV-uninfected adults with LTBI. HIV infection was associated with a lower total frequency of cytokine-producing M. tuberculosis-specific CD4 T cells, and preferential depletion of a discrete subset of M. tuberculosis-specific IFN-\u03b3+IL-2\u2212TNF-\u03b1+ CD4 T cells. M. tuberculosis-specific CD4 T cells in HIV-infected individuals expressed significantly higher levels of Ki67, compared with HIV-uninfected individuals, thus indicating recent activation and turnover of these cells in vivo. The ex vivo proliferative capacity of M. tuberculosis-specific CD4 T cells was markedly impaired in HIV-infected individuals, compared with HIV-uninfected individuals. Moreover, HIV infection was associated with increased M. tuberculosis Ag-induced CD4 T cell death ex vivo, indicating a possible mechanism contributing to impaired proliferative capacity of M. tuberculosis-specific CD4 T cells in HIV-infected individuals. These data provide new insights into the parameters of M. tuberculosis-specific CD4 T cell immunity that are impaired in HIV-infected individuals with LTBI, which may contribute to their increased risk of developing active tuberculosis disease.<\/jats:p>","DOI":"10.4049\/jimmunol.1700558","type":"journal-article","created":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:40:24Z","timestamp":1501548024000},"page":"2069-2080","source":"Crossref","is-referenced-by-count":52,"title":["HIV-1 Infection Is Associated with Depletion and Functional Impairment of <i>Mycobacterium tuberculosis<\/i>\u2013Specific CD4 T Cells in Individuals with Latent Tuberculosis Infection"],"prefix":"10.1093","volume":"199","author":[{"given":"Cheryl L","family":"Day","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA 30329"},{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A","family":"Abrahams","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town , Observatory 7925,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levelle D","family":"Harris","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"van Rooyen","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town , Observatory 7925,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynnett","family":"Stone","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town , Observatory 7925,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwou","family":"de Kock","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town , Observatory 7925,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem A","family":"Hanekom","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town , Observatory 7925,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,9,15]]},"reference":[{"key":"2025030614312890300_r1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0140-6736(10)62173-3","article-title":"Tuberculosis","volume":"378","author":"Lawn","year":"2011","journal-title":"Lancet"},{"key":"2025030614312890300_r2","volume-title":"Global Tuberculosis Report 2016.","author":"World Health Organization","year":"2016"},{"key":"2025030614312890300_r3","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1001\/jama.1995.03530020061033","article-title":"Risk factors for tuberculosis in HIV-infected persons. 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