{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:09:31Z","timestamp":1790388571596,"version":"4.1.0"},"reference-count":41,"publisher":"Frontiers Media SA","funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["IFB\/CCI: 01E01303, E:med SYSinflame: 01ZX1306F"],"award-info":[{"award-number":["IFB\/CCI: 01E01303, E:med SYSinflame: 01ZX1306F"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2017.00964","type":"journal-article","created":{"date-parts":[[2017,8,16]],"date-time":"2017-08-16T06:58:57Z","timestamp":1502866737000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":66,"title":["14\u2009Years after Discovery: Clinical Follow-up on 15 Patients with Inducible Co-Stimulator Deficiency"],"prefix":"10.3389","volume":"8","author":[{"given":"Johanna","family":"Schepp","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Skrabl-Baumgartner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Arkwright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin R.","family":"Engelhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Hambleton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Morio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehard","family":"R\u00f6ther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Warnatz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raif","family":"Geha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodo","family":"Grimbacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2017,8,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1111\/j.1365-2249.2006.03292.x","article-title":"The European internet-based patient and research database for primary immunodeficiencies: results 2004-06","volume":"147","author":"Eades-Perner","year":"2007","journal-title":"Clin Exp Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.jaci.2013.12.1077","article-title":"Clinical picture and treatment of 2212 patients with common variable immunodeficiency","volume":"134","author":"Gathmann","year":"2014","journal-title":"J Allergy Clin Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1006\/clim.1999.4725","article-title":"Common variable immunodeficiency: clinical and immunological features of 248 patients","volume":"92","author":"Cunningham-Rundles","year":"1999","journal-title":"Clin Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2","DOI":"10.4103\/2277-9175.124627","article-title":"Genetic defects and the role of helper T-cells in the pathogenesis of common variable immunodeficiency","volume":"3","author":"Sherkat","year":"2014","journal-title":"Adv Biomed Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/ni902","article-title":"Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency","volume":"4","author":"Grimbacher","year":"2003","journal-title":"Nat Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.clim.2004.07.002","article-title":"ICOS deficiency in patients with common variable immunodeficiency","volume":"113","author":"Salzer","year":"2004","journal-title":"Clin Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"5515","DOI":"10.4049\/jimmunol.0803256","article-title":"Impaired CD4 and CD8 effector function and decreased memory T cell populations in ICOS-deficient patients","volume":"182","author":"Takahashi","year":"2009","journal-title":"J Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/j.jaci.2014.12.1940","article-title":"A novel mutation in ICOS presenting as hypogammaglobulinemia with susceptibility to opportunistic pathogens","volume":"136","author":"Chou","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1007\/s10875-015-0193-x","article-title":"Astute Clinician Report: a Novel 10 bp frameshift deletion in Exon 2 of ICOS causes a combined immunodeficiency associated with an enteritis and hepatitis","volume":"35","author":"Robertson","year":"2015","journal-title":"J Clin Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/16717","article-title":"ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28","volume":"397","author":"Hutloff","year":"1999","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1038\/nri727","article-title":"The B7-CD28 superfamily","volume":"2","author":"Sharpe","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1093\/intimm\/dxf022","article-title":"A co-stimulatory molecule on activated T cells, H4\/ICOS, delivers specific signals in T(h) cells and regulates their responses","volume":"14","author":"Arimura","year":"2002","journal-title":"Int Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/S1074-7613(00)00011-X","article-title":"The CD28-related molecule ICOS is required for effective T cell-dependent immune responses","volume":"13","author":"Coyle","year":"2000","journal-title":"Immunity"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3707","DOI":"10.1002\/1521-4141(200012)30:12<3707::AID-IMMU3707>3.0.CO;2-Q","article-title":"Induction, binding specificity and function of human ICOS","volume":"30","author":"Beier","year":"2000","journal-title":"Eur J Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/S1074-7613(00)80117-X","article-title":"B7h, a novel costimulatory homolog of B7.1 and B7.2, is induced by TNFalpha","volume":"11","author":"Swallow","year":"1999","journal-title":"Immunity"},{"key":"B16","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1084\/jem.180.2.631","article-title":"Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function","volume":"180","author":"Hathcock","year":"1994","journal-title":"J Exp Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1084\/jem.20040179","article-title":"CD4+CD25+ T regulatory cells dependent on ICOS promote regulation of effector cells in the prediabetic lesion","volume":"199","author":"Herman","year":"2004","journal-title":"J Exp Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/S1074-7613(00)80195-8","article-title":"B7\/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes","volume":"12","author":"Salomon","year":"2000","journal-title":"Immunity"},{"key":"B19","doi-asserted-by":"publisher","first-page":"3045","DOI":"10.1182\/blood-2005-07-2955","article-title":"Human ICOS deficiency abrogates the germinal center reaction and provides a monogenic model for common variable immunodeficiency","volume":"107","author":"Warnatz","year":"2006","journal-title":"Blood"},{"key":"B20","doi-asserted-by":"publisher","first-page":"4927","DOI":"10.4049\/jimmunol.177.7.4927","article-title":"ICOS deficiency is associated with a severe reduction of CXCR5+CD4 germinal center Th cells","volume":"177","author":"Bossaller","year":"2006","journal-title":"J Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1084\/jem.193.12.1373","article-title":"Subspecialization of CXCR5+ T cells: B helper activity is focused in a germinal center-localized subset of CXCR5+ T cells","volume":"193","author":"Kim","year":"2001","journal-title":"J Exp Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1038\/nri1714","article-title":"Follicular B helper T cells in antibody responses and autoimmunity","volume":"5","author":"Vinuesa","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1038\/nature12058","article-title":"Follicular T-helper cell recruitment governed by bystander B cells and ICOS-driven motility","volume":"496","author":"Xu","year":"2013","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","first-page":"2680","DOI":"10.1002\/1521-4141(200209)32:9<2680::AID-IMMU2680>3.0.CO;2-6","article-title":"ICOS and CD28 reversely regulate IL-10 on re-activation of human effector T cells with mature dendritic cells","volume":"32","author":"Witsch","year":"2002","journal-title":"Eur J Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/ni.1690","article-title":"The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells","volume":"10","author":"Bauquet","year":"2009","journal-title":"Nat Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"5361","DOI":"10.4049\/jimmunol.173.9.5361","article-title":"Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6","volume":"173","author":"Ozaki","year":"2004","journal-title":"J Immunol"},{"key":"B27","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1093\/clinchem\/28.1.126","article-title":"Reference intervals for serum IgG, IgA, IgM, C3, and C4 as determined by rate nephelometry","volume":"28","author":"Jolliff","year":"1982","journal-title":"Clin Chem"},{"key":"B28","doi-asserted-by":"publisher","first-page":"3676","DOI":"10.4049\/jimmunol.169.7.3676","article-title":"Inducible costimulator costimulates cytotoxic activity and IFN-gamma production in activated murine NK cells","volume":"169","author":"Ogasawara","year":"2002","journal-title":"J Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1002\/eji.200636661","article-title":"The role of ICOS in the development of CD4 T cell help and the reactivation of memory T cells","volume":"37","author":"Mahajan","year":"2007","journal-title":"Eur J Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.jaci.2015.09.025","article-title":"The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency","volume":"137","author":"Gamez-Diaz","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1084\/jem.20061660","article-title":"Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand","volume":"204","author":"Ito","year":"2007","journal-title":"J Exp Med"},{"key":"B32","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1182\/blood-2010-11-321695","article-title":"T and B lymphocyte abnormalities in bone marrow biopsies of common variable immunodeficiency","volume":"118","author":"Ochtrop","year":"2011","journal-title":"Blood"},{"key":"B33","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1203\/00006450-200202000-00007","article-title":"Composition of precursor B-cell compartment in bone marrow from patients with X-linked agammaglobulinemia compared with healthy children","volume":"51","author":"Noordzij","year":"2002","journal-title":"Pediatr Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"774","DOI":"10.4049\/jimmunol.180.5.3613","article-title":"ICOS controls the pool size of effector-memory and regulatory T cells","volume":"180","author":"Burmeister","year":"2008","journal-title":"J Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1084\/jem.180.1.157","article-title":"gp39-CD40 interactions are essential for germinal center formation and the development of B cell memory","volume":"180","author":"Foy","year":"1994","journal-title":"J Exp Med"},{"key":"B36","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1084\/jem.20020632","article-title":"Expression of ICOS in vivo defines CD4+ effector T cells with high inflammatory potential and a strong bias for secretion of interleukin 10","volume":"197","author":"L\u00f6hning","year":"2003","journal-title":"J Exp Med"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1016\/j.jaci.2012.03.034","article-title":"TH17 deficiency in human disease","volume":"129","author":"McDonald","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1038\/sj.cr.7310106","article-title":"Expression and regulation of IL-22 in the IL-17-producing CD4+ T lymphocytes","volume":"16","author":"Chung","year":"2006","journal-title":"Cell Res"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1962","DOI":"10.4049\/jimmunol.180.3.1962","article-title":"Distinct, specific IL-17- and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response","volume":"180","author":"Scriba","year":"2008","journal-title":"J Immunol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"162","DOI":"10.3389\/fimmu.2014.00162","article-title":"Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency","volume":"5","author":"Al-Herz","year":"2014","journal-title":"Front Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1007\/s10875-015-0198-5","article-title":"The 2015 IUIS phenotypic classification for primary immunodeficiencies","volume":"35","author":"Bousfiha","year":"2015","journal-title":"J Clin Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fimmu.2017.00964\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T09:21:55Z","timestamp":1602753715000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fimmu.2017.00964\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,16]]},"references-count":41,"alternative-id":["10.3389\/fimmu.2017.00964"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2017.00964","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,16]]},"article-number":"964"}}