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Here, we used markers expressed on GCTfh, CXCR5, PD1, and ICOS, to identify potential circulating CXCR5+CD4+ Tfh-like cells (cTfh) in humans, and investigated their functional phenotypes, diversity, and ontogeny in paired donor blood and tonsils, and in blood after vaccination. Based on T cell receptor repertoire analysis, we found that PD-1\u2013expressing cTfh and tonsillar GCTfh cells were clonally related. Furthermore, an activated, antigen-specific PD1+ICOS+ cTfh subset clonally expanded after booster immunization whose frequencies correlated with vaccine-specific serum IgG; these phenotypically resembled GCTfh, and were clonally related to a resting PD1+ICOS\u2212 CD4+ memory T cell subset. Thus, we postulate that vaccination establishes clonal relatives of GCTfh within the circulating memory CD4+CXCR5+PD1+ T cell pool that expand upon reencounter of their cognate antigen.<\/jats:p>","DOI":"10.1084\/jem.20161794","type":"journal-article","created":{"date-parts":[[2017,6,21]],"date-time":"2017-06-21T14:10:48Z","timestamp":1498054248000},"page":"2139-2152","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":124,"title":["Vaccination establishes clonal relatives of germinal center T cells in the blood of humans"],"prefix":"10.1084","volume":"214","author":[{"given":"Antje","family":"Heit","sequence":"first","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, WA 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Gerdts","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Flach","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda S.","family":"Moore","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0181-3997","authenticated-orcid":true,"given":"Jonathan A.","family":"Perkins","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Washington, Seattle, WA 4"},{"name":"Seattle Children's Hospital Research Institute, Seattle, WA 8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harlan S.","family":"Robins","sequence":"additional","affiliation":[{"name":"Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 2"},{"name":"Adaptive Biotechnologies Corporation, Seattle, WA 9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4031-5499","authenticated-orcid":true,"given":"Alan","family":"Aderem","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, WA 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Spearman","sequence":"additional","affiliation":[{"name":"Pediatric Infectious Diseases, Cincinnati Children's Hospital, Cincinnati, OH 10"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia D.","family":"Tomaras","sequence":"additional","affiliation":[{"name":"Duke Human Vaccine Institute, Duke University, Durham, NC 11"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"De Rosa","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 1"},{"name":"Department of Laboratory Medicine, University of Washington, Seattle, WA 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2276-7117","authenticated-orcid":true,"given":"M. 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