{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:18:26Z","timestamp":1758709106048,"version":"3.40.4"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["; R01AI142647"],"award-info":[{"award-number":["; R01AI142647"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD023412"],"award-info":[{"award-number":["R01HD023412"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Emory\/Georgia TB Research Advancement Center","award":["P30AI168386"],"award-info":[{"award-number":["P30AI168386"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Despite immune restoration after initiation of antiretroviral treatment (ART), the risk of tuberculosis (TB) persists in children with HIV (CHIV). We determined patterns of immune restoration of mycobacteria-specific T cells following ART in CHIV.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>CD4 and CD8 T-cell activation and memory phenotype and functional profiles before and 6 months after ART were evaluated in peripheral blood mononuclear cells from CHIV enrolled in the PUSH study (NCT02063880) in Nairobi, Kenya. T-cell expression of cytokines and activation-induced markers were measured following stimulation of peripheral blood mononuclear cells with a pool of 300 peptides from TB (MTB300) or staphylococcal enterotoxin B.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among 47 CHIV (median age, 1.5 years), staphylococcal enterotoxin B\u2013induced Th1 cytokine+ and activation-induced marker+ CD4 cell frequencies increased significantly after 6 months of ART. Although MTB300-specific CD4 and CD8 cell frequency did not increase after ART, polyfunctional capacity of MTB300-specific CD4 cells expressing combinations of Th1 cytokines with CD40L increased significantly after ART. Baseline age, immune activation, and effector memory CD4 levels were associated with less restoration of MTB300-specific polyfunctional CD4 cells, whereas CD4 percentage and levels of naive CD4 cells following ART were associated with improved MTB300-specific polyfunctional capacity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Despite increases in Th1 cytokine production, deficits in mycobacteria-specific CD4 cells persisted 6 months after ART, with higher deficits in older CHIV with more immunosuppression, higher immune activation, and lower proportion of naive CD4 cells. These findings may explain persistent TB risk during early ART among CHIV and identify those at highest risk.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiae630","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T17:44:07Z","timestamp":1734543847000},"page":"957-966","source":"Crossref","is-referenced-by-count":1,"title":["Patterns and Cofactors of Polyfunctional Mycobacteria-Specific T-Cell Response Restoration Following 6-Month Antiretroviral Treatment in Children With HIV"],"prefix":"10.1093","volume":"231","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6497-4846","authenticated-orcid":false,"given":"Cheryl L","family":"Day","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine"},{"name":"Emory Vaccine Center, Emory University , Atlanta, Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene N","family":"Njuguna","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Kenyatta National Hospital , Nairobi ,","place":["Kenya"]},{"name":"Department of Global Health, University of Washington , Seattle"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa Marie","family":"Cranmer","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine , Atlanta"},{"name":"Children's Healthcare of Atlanta , Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy E","family":"Whatney","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine"},{"name":"Emory Vaccine Center, Emory University , Atlanta, Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel A","family":"Pearson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine"},{"name":"Emory Vaccine Center, Emory University , Atlanta, Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia S","family":"Lindestam Arlehamn","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology , California"},{"name":"Center for Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut , Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Sette","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology , California"},{"name":"Department of Medicine, University of California San Diego"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9809-5997","authenticated-orcid":false,"given":"Sylvia M","family":"LaCourse","sequence":"additional","affiliation":[{"name":"Department of Global Health, University of Washington , Seattle"},{"name":"Division of Allergy and Infectious Diseases, Department of Medicine"},{"name":"Department of Epidemiology, University of Washington , Seattle"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3513-774X","authenticated-orcid":false,"given":"Jaclyn N","family":"Escudero","sequence":"additional","affiliation":[{"name":"Department of Global Health, University of Washington , Seattle"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loren E","family":"Sasser","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine"},{"name":"Emory Vaccine Center, Emory University , Atlanta, Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7516-2168","authenticated-orcid":false,"given":"Cyrus","family":"Mugo","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Kenyatta National Hospital , Nairobi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8862-3058","authenticated-orcid":false,"given":"Hellen Moraa","family":"Okinyi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, University of Nairobi ,","place":["Kenya"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Maleche-Obimbo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, University of Nairobi ,","place":["Kenya"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalton C","family":"Wamalwa","sequence":"additional","affiliation":[{"name":"Department of 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