{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T08:39:39Z","timestamp":1774773579332,"version":"3.50.1"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":1558,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>HIV infection is a significant risk factor for reactivation of latent Mycobacterium tuberculosis infection (LTBI) and progression to active tuberculosis disease, yet the mechanisms whereby HIV impairs T cell immunity to M. tuberculosis have not been fully defined. Evaluation of M. tuberculosis\u2013specific CD4 T cells is commonly based on IFN-\u03b3 production, yet increasing evidence indicates the immune response to M. tuberculosis is heterogeneous and encompasses IFN-\u03b3\u2013independent responses. We hypothesized that upregulation of surface activation-induced markers (AIM) would facilitate detection of human M. tuberculosis\u2013specific CD4 T cells in a cytokine-independent manner in HIV-infected and HIV-uninfected individuals with LTBI. PBMCs from HIV-infected and HIV-uninfected adults in Kenya were stimulated with CFP-10 and ESAT-6 peptides and evaluated by flow cytometry for upregulation of the activation markers CD25, OX40, CD69, and CD40L. Although M. tuberculosis\u2013specific IFN-\u03b3 and IL-2 production was dampened in HIV-infected individuals, M. tuberculosis\u2013specific CD25+OX40+ and CD69+CD40L+ CD4 T cells were detectable in the AIM assay in both HIV-uninfected and HIV-infected individuals with LTBI. Importantly, the frequency of M. tuberculosis\u2013specific AIM+ CD4 T cells was not directly impacted by HIV viral load or CD4 count, thus demonstrating the feasibility of AIM assays for analysis of M. tuberculosis\u2013specific CD4 T cells across a spectrum of HIV infection states. These data indicate that AIM assays enable identification of M. tuberculosis\u2013specific CD4 T cells in a cytokine-independent manner in HIV-uninfected and HIV-infected individuals with LTBI in a high-tuberculosis burden setting, thus facilitating studies to define novel T cell correlates of protection to M. tuberculosis and elucidate mechanisms of HIV-associated dysregulation of antimycobacterial immunity.<\/jats:p>","DOI":"10.4049\/immunohorizons.2000051","type":"journal-article","created":{"date-parts":[[2020,10,2]],"date-time":"2020-10-02T19:00:12Z","timestamp":1601665212000},"page":"573-584","source":"Crossref","is-referenced-by-count":19,"title":["Activation-Induced Marker Expression Identifies <i>Mycobacterium tuberculosis<\/i>\u2013Specific CD4 T Cells in a Cytokine-Independent Manner in HIV-Infected Individuals with Latent Tuberculosis"],"prefix":"10.1093","volume":"4","author":[{"given":"Morgan S","family":"Barham","sequence":"first","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30329"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy E","family":"Whatney","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30329"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremiah","family":"Khayumbi","sequence":"additional","affiliation":[{"name":"Center for Global Health Research, Kenya Medical Research Institute , Kisumu 40100 ,","place":["Kenya"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua","family":"Ongalo","sequence":"additional","affiliation":[{"name":"Center for Global Health Research, Kenya Medical Research Institute , Kisumu 40100 ,","place":["Kenya"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loren E","family":"Sasser","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30329"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3990-3656","authenticated-orcid":false,"given":"Angela","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Rollins School of Public Health, Emory University , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meghan","family":"Franczek","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Rollins School of Public Health, Emory University , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mbuyi Madeleine","family":"Kabongo","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Rollins School of Public Health, Emory University , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3559-9028","authenticated-orcid":false,"given":"Samuel G","family":"Ouma","sequence":"additional","affiliation":[{"name":"Center for Global Health Research, Kenya Medical Research Institute , Kisumu 40100 ,","place":["Kenya"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix Odhiambo","family":"Hayara","sequence":"additional","affiliation":[{"name":"Center for Global Health Research, Kenya Medical Research Institute , Kisumu 40100 ,","place":["Kenya"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neel R","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Rollins School of Public Health, Emory University , Atlanta, GA 30322"},{"name":"Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6497-4846","authenticated-orcid":false,"given":"Cheryl L","family":"Day","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30329"},{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,10,5]]},"reference":[{"key":"2025010608424086800_r1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1002152","article-title":"The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling","volume":"13","author":"Houben","year":"2016","journal-title":"PLoS Med."},{"key":"2025010608424086800_r2","volume-title":"Global Tuberculosis Report 2019","author":"World Health 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