{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T13:41:47Z","timestamp":1776778907270,"version":"3.51.2"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2019,1,8]],"date-time":"2019-01-08T00:00:00Z","timestamp":1546905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT104748MA"],"award-info":[{"award-number":["WT104748MA"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,4,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Susceptibility to coinfections in human immunodeficiency virus (HIV)-infected patients remains increased despite antiretroviral therapy (ART). To elucidate mechanisms involved in immune reconstitution, we studied immune activation, immune exhaustion, and HIV- and copathogen-specific T-cell responses in children before and after ART.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We prospectively enrolled 25 HIV-infected children to study HIV-, cytomegalovirus (CMV)-, and tuberculosis (TB)-specific T-cell responses before and 1 year after initiation of ART using intracellular cytokine (interleukin-2, interferon-\u03b3, tumor necrosis factor-\u03b1) staining assays after in vitro stimulation. We further measured expression of activation, immune exhaustion, and memory phenotype markers and studied proliferative responses after antigen stimulation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We observed differential, pathogen-specific changes after 1 year of ART in cytokine profiles of CD4 T-cell responses that were associated with shifts in memory phenotype and decreased programmed cell death 1 (PD-1) expression. The proliferative capacity of HIV- and PPD-specific responses increased after 1 year of ART. Of note, the recovery of CMV- and TB-specific responses was correlated with a decrease in PD-1 expression (r = 0.83, P = .008 and r = 0.81, P = .0007, respectively).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Reconstitution of immune responses on ART is associated with alterations in T-cell phenotype, function, and PD-1 expression that are distinct for HIV, TB, and CMV. The PD-1 pathway represents a potential target for immunotherapy in HIV-infected patients on ART with insufficient immune reconstitution.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiy668","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T07:07:43Z","timestamp":1545203263000},"page":"1407-1417","source":"Crossref","is-referenced-by-count":13,"title":["Differential Pathogen-Specific Immune Reconstitution in Antiretroviral Therapy-Treated Human Immunodeficiency Virus-Infected Children"],"prefix":"10.1093","volume":"219","author":[{"given":"Maximilian","family":"Muenchhoff","sequence":"first","affiliation":[{"name":"Department of Paediatrics, University of Oxford, Peter Medawar Building for Pathogen Research, South Parks Road, United Kingdom"},{"name":"HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"},{"name":"Max von Pettenkofer Institute, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU M\u00fcnchen, Munich, Germany"},{"name":"German Center for Infection Research (DZIF), partner site Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Adland","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Oxford, Peter Medawar Building for Pathogen Research, South Parks Road, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Roider","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Oxford, Peter Medawar Building for Pathogen Research, South Parks Road, United Kingdom"},{"name":"HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"},{"name":"Department of Infectious Diseases, Ludwig-Maximilians-University, Munich"},{"name":"Africa Health Research Institute (AHRI), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Kl\u00f8verpris","sequence":"additional","affiliation":[{"name":"Africa Health Research Institute (AHRI), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"},{"name":"Department of Immunology and Microbiology, University of Copenhagen, Denmark"},{"name":"8Department of Infection and Immunity, University College London, United Kingdom"},{"name":"Max Planck Institute for Infection Biology, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alasdair","family":"Leslie","sequence":"additional","affiliation":[{"name":"Africa Health Research Institute (AHRI), Nelson R. 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