{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:08:58Z","timestamp":1791295738282,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2008,11,1]],"date-time":"2008-11-01T00:00:00Z","timestamp":1225497600000},"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":[[2008,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Tuberculosis-associated immune reconstitution inflammatory syndrome (TB\u2013IRIS) induced by combination antiretroviral therapy (cART) has been attributed to dysregulated expansion of tuberculin PPD\u2013specific IFN-\u03b3\u2013secreting CD4+ T cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate the role of type 1 helper T cell expansions and regulatory T cells in HIV\u2013TB IRIS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Longitudinal and cross-sectional studies of Mycobacterium tuberculosis\u2013specific IFN-\u03b3 enzyme-linked immunospot responses and flow cytometric analysis of blood cells from a total of 129 adults with HIV-1\u2013associated tuberculosis, 98 of whom were prescribed cART.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>In cross-sectional analysis the frequency of IFN-\u03b3\u2013secreting T cells recognizing early secretory antigenic target (ESAT)-6, \u03b1-crystallins 1 and 2, and PPD of M. tuberculosis was higher in patients with TB\u2013IRIS than in similar patients treated for both HIV-1 and tuberculosis who did not develop IRIS (non-IRIS; P \u2264 0.03). The biggest difference was in the recognition of \u03b1-crystallin molecules: peptide mapping indicated a polyclonal response. Flow cytometric analysis indicated equal proportions of CD4+ and CD8+ cells positive for activation markers HLA-DR and CD71 in both patients with TB\u2013IRIS and non-IRIS patients. The percentage of CD4+ cells positive for FoxP3 (Forkhead box P3) was low in both groups (TB\u2013IRIS, 5.3 \u00b1 4.5; non-IRIS, 2.46 \u00b1 2.46; P = 0.13). Eight weeks of longitudinal analysis of patients with tuberculosis who were starting cART showed dynamic changes in antigen-specific IFN-\u03b3\u2013secreting T cells in both the TB\u2013IRIS and non-IRIS groups: the only significant trend was an increased response to PPD in the TB\u2013IRIS group (P = 0.041).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>There is an association between helper T-cell type 1 expansions and TB\u2013IRIS, but the occurrence of similar expansions in non-IRIS brings into question whether these are causal. The defect in immune regulation responsible for TB\u2013IRIS remains to be fully elucidated.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.200806-858oc","type":"journal-article","created":{"date-parts":[[2008,11,5]],"date-time":"2008-11-05T16:53:14Z","timestamp":1225903994000},"page":"1083-1089","source":"Crossref","is-referenced-by-count":121,"title":["Type 1 Helper T Cells and FoxP3-positive T Cells in HIV\u2013Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome"],"prefix":"10.1093","volume":"178","author":[{"given":"Graeme","family":"Meintjes","sequence":"first","affiliation":[{"name":"Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"GF Jooste Hospital, Manenberg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin Andrea","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"National Institute for Medical Research, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molebogeng Xheeda","family":"Rangaka","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keira","family":"Skolimowska","sequence":"additional","affiliation":[{"name":"GF Jooste Hospital, Manenberg, South Africa"},{"name":"Division of Medicine, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerryn","family":"van Veen","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musaed","family":"Abrahams","sequence":"additional","affiliation":[{"name":"Provincial Administration of the Western Cape, Khayelitsha, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronnett","family":"Seldon","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique J.","family":"Pepper","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"GF Jooste Hospital, Manenberg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Rebe","sequence":"additional","affiliation":[{"name":"GF Jooste Hospital, Manenberg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla","family":"Mouton","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"van Cutsem","sequence":"additional","affiliation":[{"name":"M\u00e9dicins sans Fronti\u00e9res, Khayelitsha, South Africa; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark Patrick","family":"Nicol","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Maartens","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert John","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"GF Jooste Hospital, Manenberg, South Africa"},{"name":"National Institute for Medical Research, London, United Kingdom"},{"name":"Division of Medicine, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,11,15]]},"reference":[{"key":"2026032102314285500_BIB1","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1016\/S0140-6736(07)61262-8","volume":"370","year":"2007","journal-title":"Lancet"},{"key":"2026032102314285500_BIB2","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1016\/S0140-6736(02)08904-3","volume":"359","year":"2002","journal-title":"Lancet"},{"key":"2026032102314285500_BIB3","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1086\/522986","volume":"45","year":"2007","journal-title":"Clin Infect Dis"},{"key":"2026032102314285500_BIB4","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1097\/01.aids.0000194808.20035.c1","volume":"19","year":"2005","journal-title":"AIDS"},{"key":"2026032102314285500_BIB5","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1126\/science.277.5322.112","volume":"277","year":"1997","journal-title":"Science"},{"key":"2026032102314285500_BIB6","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1111\/j.1365-3024.2006.00900.x","volume":"28","year":"2006","journal-title":"Parasite Immunol"},{"key":"2026032102314285500_BIB7","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1164\/rccm.200709-1311PP","volume":"177","year":"2008","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102314285500_BIB8","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1164\/ajrccm.158.1.9712001","volume":"158","year":"1998","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102314285500_BIB9","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1097\/00002030-199211000-00009","volume":"6","year":"1992","journal-title":"AIDS"},{"key":"2026032102314285500_BIB10","doi-asserted-by":"crossref","first-page":"191","DOI":"10.2165\/00003495-200868020-00004","volume":"68","year":"2008","journal-title":"Drugs"},{"key":"2026032102314285500_BIB11","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1136\/thx.2003.019224","volume":"59","year":"2004","journal-title":"Thorax"},{"key":"2026032102314285500_BIB12","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1086\/499356","volume":"42","year":"2006","journal-title":"Clin Infect Dis"},{"key":"2026032102314285500_BIB13","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1097\/QAD.0b013e328011efac","volume":"21","year":"2007","journal-title":"AIDS"},{"key":"2026032102314285500_BIB14","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1097\/QAD.0b013e3282f4a607","volume":"22","year":"2008","journal-title":"AIDS"},{"key":"2026032102314285500_BIB15","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1089\/088922202760265632","volume":"18","year":"2002","journal-title":"AIDS Res Hum Retroviruses"},{"key":"2026032102314285500_BIB16","doi-asserted-by":"crossref","first-page":"F1","DOI":"10.1097\/01.aids.0000202648.18526.bf","volume":"20","year":"2006","journal-title":"AIDS"},{"key":"2026032102314285500_BIB17","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1742-6405-5-9","volume":"5","year":"2008","journal-title":"AIDS Res Ther"},{"key":"2026032102314285500_BIB18","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1097\/QAD.0b013e3280b079c8","volume":"21","year":"2007","journal-title":"AIDS"},{"key":"2026032102314285500_BIB19","year":"2007"},{"key":"2026032102314285500_BIB20","year":"2008"},{"key":"2026032102314285500_BIB21","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/S1473-3099(08)70184-1","volume":"8","year":"2008","journal-title":"Lancet Infect Dis"},{"key":"2026032102314285500_BIB22","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/S1473-3099(03)00609-1","volume":"3","year":"2003","journal-title":"Lancet Infect Dis"},{"key":"2026032102314285500_BIB23","year":"2006"},{"key":"2026032102314285500_BIB24","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1086\/518234","volume":"44","year":"2007","journal-title":"Clin Infect Dis"},{"key":"2026032102314285500_BIB25","doi-asserted-by":"crossref","first-page":"4237","DOI":"10.4049\/jimmunol.174.7.4237","volume":"174","year":"2005","journal-title":"J Immunol"},{"key":"2026032102314285500_BIB26","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1128\/iai.63.5.1710-1717.1995","volume":"63","year":"1995","journal-title":"Infect Immun"},{"key":"2026032102314285500_BIB27","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1164\/rccm.200402-232OC","volume":"170","year":"2004","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102314285500_BIB28","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1128\/jcm.35.3.553-557.1997","volume":"35","year":"1997","journal-title":"J Clin Microbiol"},{"key":"2026032102314285500_BIB29","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1086\/515336","volume":"178","year":"1998","journal-title":"J Infect Dis"},{"key":"2026032102314285500_BIB30","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1046\/j.1365-3083.1998.00420.x","volume":"48","year":"1998","journal-title":"Scand J Immunol"},{"key":"2026032102314285500_BIB31","doi-asserted-by":"crossref","first-page":"7534","DOI":"10.1073\/pnas.121172498","volume":"98","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026032102314285500_BIB32","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1111\/j.1365-2958.2004.04450.x","volume":"55","year":"2005","journal-title":"Mol Microbiol"},{"key":"2026032102314285500_BIB33","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1086\/429245","volume":"40","year":"2005","journal-title":"Clin Infect Dis"},{"key":"2026032102314285500_BIB34","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1128\/CVI.00041-07","volume":"14","year":"2007","journal-title":"Clin Vaccine Immunol"},{"key":"2026032102314285500_BIB35","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1164\/rccm.200610-1439OC","volume":"175","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102314285500_BIB36","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1164\/rccm.200508-1294OC","volume":"173","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102314285500_BIB37","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1164\/rccm.200701-084OC","volume":"176","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032102314285500_BIB38","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1084\/jem.20062105","volume":"204","year":"2007","journal-title":"J Exp Med"},{"key":"2026032102314285500_BIB39","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1097\/00002030-200404090-00006","volume":"18","year":"2004","journal-title":"AIDS"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/178\/10\/1083\/67445044\/ajrccm_178_10_1083.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/178\/10\/1083\/67445044\/ajrccm_178_10_1083.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T06:31:49Z","timestamp":1774074709000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/178\/10\/1083\/8525961"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,11]]},"references-count":39,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2008,11,15]]},"published-print":{"date-parts":[[2008,11,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.200806-858oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2008,11]]},"published":{"date-parts":[[2008,11]]}}}