{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T10:07:58Z","timestamp":1767866878353,"version":"3.49.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"4","funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2016\u201303052"],"award-info":[{"award-number":["2016\u201303052"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Swedish Cancer Society","doi-asserted-by":"publisher","award":["CAN 2017\/777"],"award-info":[{"award-number":["CAN 2017\/777"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK108350"],"award-info":[{"award-number":["R01DK108350"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN261200800001E"],"award-info":[{"award-number":["HHSN261200800001E"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["75N910D00024"],"award-info":[{"award-number":["75N910D00024"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["75N91019F00131"],"award-info":[{"award-number":["75N91019F00131"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Mucosal-associated invariant T (MAIT) cells constitute a subset of unconventional, MR1-restricted T cells involved in antimicrobial responses as well as inflammatory, allergic, and autoimmune diseases. Chronic infection and inflammatory disorders as well as immunodeficiencies are often associated with decline and\/or dysfunction of MAIT cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We investigated the MAIT cells in patients with idiopathic CD4+ lymphocytopenia (ICL), a syndrome characterized by consistently low CD4 T-cell counts (&amp;lt;300 cell\/\u00b5L) in the absence of HIV infection or other known immunodeficiency, and by susceptibility to certain opportunistic infections.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The numbers, phenotype, and function of MAIT cells in peripheral blood were preserved in ICL patients compared to healthy controls. Administration of interleukin-7 (IL-7) to ICL patients expanded the CD8+ MAIT-cell subset, with maintained responsiveness and effector functions after IL-7 treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>ICL patients maintain normal levels and function of MAIT cells, preserving some antibacterial responses despite the deficiency in CD4+ T cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT00867269.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaa782","type":"journal-article","created":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T07:59:43Z","timestamp":1608364783000},"page":"715-725","source":"Crossref","is-referenced-by-count":5,"title":["Preserved Mucosal-Associated Invariant T-Cell Numbers and Function in Idiopathic CD4 Lymphocytopenia"],"prefix":"10.1093","volume":"224","author":[{"given":"Ornella","family":"Sortino","sequence":"first","affiliation":[{"name":"Clinical Research Directorate\/Clinical Monitoring Leidos Research Program, Leidos Biomedical Research, Inc., National Cancer Institute Campus at Frederick, Frederick, Maryland, USA"},{"name":"National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joana","family":"Dias","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Anderson","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Laidlaw","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edwin","family":"Leeansyah","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden"},{"name":"Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Lisco","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia","family":"Sheikh","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan K","family":"Sandberg","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0076-0224","authenticated-orcid":false,"given":"Irini","family":"Sereti","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,12,24]]},"reference":[{"key":"2021081613474803900_CIT0001","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/ni.1890","article-title":"Antimicrobial activity of mucosal-associated invariant T cells","volume":"11","author":"Le Bourhis","year":"2010","journal-title":"Nat Immunol"},{"key":"2021081613474803900_CIT0002","doi-asserted-by":"crossref","first-page":"e1005072","DOI":"10.1371\/journal.ppat.1005072","article-title":"Arming of MAIT cell cytolytic antimicrobial activity is induced by IL-7 and defective in HIV-1 infection","volume":"11","author":"Leeansyah","year":"2015","journal-title":"PLoS Pathog"},{"key":"2021081613474803900_CIT0003","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1146\/annurev-immunol-080719-015428","article-title":"MAIT cells in health and disease","volume":"38","author":"Provine","year":"2020","journal-title":"Annu Rev Immunol"},{"key":"2021081613474803900_CIT0004","doi-asserted-by":"crossref","first-page":"E5434","DOI":"10.1073\/pnas.1705759114","article-title":"Multiple layers of heterogeneity and subset diversity in human MAIT cell responses to distinct microorganisms and to innate cytokines","volume":"114","author":"Dias","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2021081613474803900_CIT0005","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.4049\/jimmunol.1004006","article-title":"The BTB-ZF family of transcription factors: key regulators of lineage commitment and effector function development in the immune system","volume":"187","author":"Beaulieu","year":"2011","journal-title":"J Immunol"},{"key":"2021081613474803900_CIT0006","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.immuni.2008.07.011","article-title":"The transcription factor PLZF directs the effector program of the NKT cell lineage","volume":"29","author":"Savage","year":"2008","journal-title":"Immunity"},{"key":"2021081613474803900_CIT0007","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/ni.1641","article-title":"The BTB-zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions","volume":"9","author":"Kovalovsky","year":"2008","journal-title":"Nat Immunol"},{"key":"2021081613474803900_CIT0008","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1182\/blood-2010-08-303339","article-title":"Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells","volume":"117","author":"Dusseaux","year":"2011","journal-title":"Blood"},{"key":"2021081613474803900_CIT0009","doi-asserted-by":"crossref","first-page":"e54","DOI":"10.1371\/journal.pbio.1000054","article-title":"Stepwise development of MAIT cells in mouse and human","volume":"7","author":"Martin","year":"2009","journal-title":"PLoS Biol"},{"key":"2021081613474803900_CIT0010","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/mi.2016.30","article-title":"MAIT cells reside in the female genital mucosa and are biased towards IL-17 and IL-22 production in response to bacterial stimulation","volume":"10","author":"Gibbs","year":"2017","journal-title":"Mucosal Immunol"},{"key":"2021081613474803900_CIT0011","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1084\/jem.20130958","article-title":"Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells","volume":"210","author":"Reantragoon","year":"2013","journal-title":"J Exp Med"},{"key":"2021081613474803900_CIT0012","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1038\/ncomms4143","article-title":"Acquisition of innate-like microbial reactivity in mucosal tissues during human fetal MAIT-cell development","volume":"5","author":"Leeansyah","year":"2014","journal-title":"Nat Commun"},{"key":"2021081613474803900_CIT0013","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/s41577-019-0191-y","article-title":"Mucosal-associated invariant T cells and disease","volume":"19","author":"Toubal","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"2021081613474803900_CIT0014","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1182\/blood-2012-07-445429","article-title":"Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection","volume":"121","author":"Leeansyah","year":"2013","journal-title":"Blood"},{"key":"2021081613474803900_CIT0015","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1182\/blood-2012-06-436436","article-title":"Early and nonreversible decrease of CD161++\/MAIT cells in HIV infection","volume":"121","author":"Cosgrove","year":"2013","journal-title":"Blood"},{"key":"2021081613474803900_CIT0016","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1056\/NEJM199302113280601","article-title":"Unexplained opportunistic infections and CD4+ T-lymphocytopenia without HIV infection. an investigation of cases in the United States. The Centers for Disease Control Idiopathic CD4+ T-Lymphocytopenia Task Force","volume":"328","author":"Smith","year":"1993","journal-title":"N Engl J Med"},{"key":"2021081613474803900_CIT0017","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1182\/blood-2007-12-127878","article-title":"Idiopathic CD4+ lymphocytopenia: natural history and prognostic factors","volume":"112","author":"Zonios","year":"2008","journal-title":"Blood"},{"key":"2021081613474803900_CIT0018","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1093\/infdis\/jiv282","article-title":"T-cell depletion in the colonic mucosa of patients with idiopathic CD4+ lymphopenia","volume":"212","author":"Kovacs","year":"2015","journal-title":"J Infect Dis"},{"key":"2021081613474803900_CIT0019","doi-asserted-by":"crossref","first-page":"5326","DOI":"10.1172\/JCI136254","article-title":"Prevalence and pathogenicity of autoantibodies in patients with idiopathic CD4 lymphopenia","volume":"130","author":"Perez-Diez","year":"2020","journal-title":"J Clin Invest"},{"key":"2021081613474803900_CIT0020","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1182\/blood-2015-05-645077","article-title":"Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia","volume":"127","author":"Sheikh","year":"2016","journal-title":"Blood"},{"key":"2021081613474803900_CIT0021","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1097\/QAD.0000000000001760","article-title":"IL-7 treatment supports CD8+ mucosa-associated invariant T-cell restoration in HIV-1-infected patients on antiretroviral therapy","volume":"32","author":"Sortino","year":"2018","journal-title":"AIDS"},{"key":"2021081613474803900_CIT0022","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/978-1-4939-6548-9_17","article-title":"Extensive phenotypic analysis, transcription factor profiling, and effector cytokine production of human MAIT cells by flow cytometry","volume":"1514","author":"Dias","year":"2017","journal-title":"Methods Mol Biol"},{"key":"2021081613474803900_CIT0023","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1189\/jlb.4TA0815-391RR","article-title":"Human MAIT-cell responses to Escherichia coli: activation, cytokine production, proliferation, and cytotoxicity","volume":"100","author":"Dias","year":"2016","journal-title":"J Leukoc Biol"},{"key":"2021081613474803900_CIT0024","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.3389\/fimmu.2018.01333","article-title":"Mucosal-associated invariant T cells in autoimmune diseases","volume":"9","author":"Chiba","year":"2018","journal-title":"Front Immunol"},{"key":"2021081613474803900_CIT0025","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/s41467-019-13975-9","article-title":"Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection","volume":"11","author":"Lal","year":"2020","journal-title":"Nat Commun"},{"key":"2021081613474803900_CIT0026","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1093\/infdis\/jis219","article-title":"Decreased interleukin 7 responsiveness of T lymphocytes in patients with idiopathic CD4 lymphopenia","volume":"205","author":"Puronen","year":"2012","journal-title":"J Infect Dis"},{"key":"2021081613474803900_CIT0027","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1189\/jlb.4A1215-581R","article-title":"Interleukin 7 immunotherapy improves host immunity and survival in a two-hit model of Pseudomonas aeruginosa pneumonia","volume":"101","author":"Shindo","year":"2017","journal-title":"J Leukoc Biol"},{"key":"2021081613474803900_CIT0028","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1097\/MD.0000000000000017","article-title":"Idiopathic CD4 lymphocytopenia: clinical and immunologic characteristics and follow-up of 40 patients","volume":"93","author":"R\u00e9gent","year":"2014","journal-title":"Medicine (Baltimore)"},{"key":"2021081613474803900_CIT0029","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1159\/000053800","article-title":"Lymphocyte diversity in a 9-year-old boy with idiopathic CD4+ T cell lymphocytopenia","volume":"125","author":"Fr\u00fchwirth","year":"2001","journal-title":"Int Arch Allergy Immunol"},{"key":"2021081613474803900_CIT0030","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1051\/jbio\/1999193010011","article-title":"Deficiency of the CD3-TCR signal pathway in three patients with idiopathic CD4+ lymphocytopenia","volume":"193","author":"Hubert","year":"1999","journal-title":"J Soc Biol"},{"key":"2021081613474803900_CIT0031","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1159\/000084258","article-title":"Idiopathic CD4+ lymphocytopenia may be due to decreased bone marrow clonogenic capability","volume":"136","author":"Isgr\u00f2","year":"2005","journal-title":"Int Arch Allergy Immunol"},{"key":"2021081613474803900_CIT0032","doi-asserted-by":"crossref","first-page":"3708","DOI":"10.1182\/blood-2009-02-202796","article-title":"Idiopathic CD4+ T-cell lymphocytopenia is associated with impaired membrane expression of the chemokine receptor CXCR4","volume":"115","author":"Scott-Algara","year":"2010","journal-title":"Blood"},{"key":"2021081613474803900_CIT0033","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1038\/ni.3565","article-title":"A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage","volume":"17","author":"Koay","year":"2016","journal-title":"Nat Immunol"},{"key":"2021081613474803900_CIT0034","doi-asserted-by":"crossref","first-page":"3967","DOI":"10.1038\/s41467-018-05528-3","article-title":"Hallmarks of primate lentiviral immunodeficiency infection recapitulate loss of innate lymphoid cells","volume":"9","author":"Mudd","year":"2018","journal-title":"Nat Commun"},{"key":"2021081613474803900_CIT0035","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1084\/jem.20171739","article-title":"Ontogeny of human mucosal-associated invariant T cells and related T cell subsets","volume":"215","author":"Ben Youssef","year":"2018","journal-title":"J Exp Med"},{"key":"2021081613474803900_CIT0036","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.4049\/jimmunol.176.3.1618","article-title":"MR1-restricted V alpha 19i mucosal-associated invariant T cells are innate T cells in the gut lamina propria that provide a rapid and diverse cytokine response","volume":"176","author":"Kawachi","year":"2006","journal-title":"J Immunol"},{"key":"2021081613474803900_CIT0037","doi-asserted-by":"crossref","first-page":"e3000644","DOI":"10.1371\/journal.pbio.3000644","article-title":"Human MAIT cell cytolytic effector proteins synergize to overcome carbapenem resistance in Escherichia coli","volume":"18","author":"Boulouis","year":"2020","journal-title":"PLoS Biol"},{"key":"2021081613474803900_CIT0038","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/eji.201343509","article-title":"CD161++CD8+ T cells, including the MAIT cell subset, are specifically activated by IL-12 + IL-18 in a TCR-independent manner","volume":"44","author":"Ussher","year":"2014","journal-title":"Eur J Immunol"},{"key":"2021081613474803900_CIT0039","doi-asserted-by":"crossref","first-page":"E3119","DOI":"10.1073\/pnas.1302799110","article-title":"MAIT cells are critical for optimal mucosal immune responses during in vivo pulmonary bacterial infection","volume":"110","author":"Meierovics","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2021081613474803900_CIT0040","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.1016\/j.chest.2018.01.020","article-title":"Severely impaired control of bacterial infections in a patient with cystic fibrosis defective in mucosal-associated invariant T cells","volume":"153","author":"Pincikova","year":"2018","journal-title":"Chest"},{"key":"2021081613474803900_CIT0041","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1097\/QAD.0b013e32833a3967","article-title":"AIDS-defining opportunistic illnesses in US patients, 1994\u20132007: a cohort study","volume":"24","author":"Buchacz","year":"2010","journal-title":"AIDS"},{"key":"2021081613474803900_CIT0042","doi-asserted-by":"crossref","first-page":"142","DOI":"10.4049\/immunohorizons.1700039","article-title":"Loss of circulating mucosal-associated invariant T cells in common variable immunodeficiency is associated with immune activation and loss EOMES and PLZF","volume":"1","author":"Paquin-Proulx","year":"2017","journal-title":"ImmunoHorizons"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiaa782\/38625101\/jiaa782.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jid\/article-pdf\/224\/4\/715\/39761330\/jiaa782.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jid\/article-pdf\/224\/4\/715\/39761330\/jiaa782.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T13:50:16Z","timestamp":1629121816000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/224\/4\/715\/6047591"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,24]]},"references-count":42,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,12,24]]},"published-print":{"date-parts":[[2021,8,16]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiaa782","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,8,15]]},"published":{"date-parts":[[2020,12,24]]}}}