{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T05:45:11Z","timestamp":1761630311825},"reference-count":35,"publisher":"American Society of Hematology","issue":"9","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To investigate the mechanisms of human T-cell reconstitution following allogeneic hemopoietic stem cell transplantation (alloSCT), we analyzed the clonal composition of human cytomegalovirus (HCMV)-specific or Epstein-Barr virus (EBV)-specific CD8+ T cells in 10 alloSC transplant recipients and their donors. All virus-specific CD8+ T-cell clones isolated from recipients after alloSCT contained DNA of donor origin. In all 6 D+\/R+ sibling alloSCTs from seropositive donors into seropositive recipients, donor virus-specific clones transferred in the allograft underwent early expansion and were maintained long term in the recipient. In contrast, in 2 of 3 HCMV D+\/R- alloSC transplant recipients in whom there was no detectable HCMV infection, donor HCMV-specific clones were undetectable, whereas donor EBV-specific clones were maintained in the same EBV-seropositive recipients, suggesting that transferred clones require antigen for their maintenance. Following D-\/R+ transplantation from 3 seronegative donors into seropositive recipients, a delayed primary virus-specific CD8+ T-cell response was observed, in which the T cells contained donor DNA, suggesting that new antigen-specific T cells arose in the recipient from donor-derived progenitors. In 2 of 4 HCMV D+\/R+ sibling allograft recipients the clonal composition underwent diversification as compared with their donors, with delayed persistent expansion of HCMV-specific clones that were undetectable in the donor or in the recipient during the early months after transplantation; this diversification may represent expansion of new clones generated from donor-derived progenitors. We conclude that, following alloSCT, late diversification of the HCMV-specific CD8+ T-cell clonal repertoire can occur in response to persistent viral antigen.<\/jats:p>","DOI":"10.1182\/blood-2002-12-3689","type":"journal-article","created":{"date-parts":[[2003,7,22]],"date-time":"2003-07-22T00:24:13Z","timestamp":1058833453000},"page":"3427-3438","update-policy":"http:\/\/dx.doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":52,"title":["Late diversification in the clonal composition of human cytomegalovirus-specific CD8+ T cells following allogeneic hemopoietic stem cell transplantation"],"prefix":"10.1182","volume":"102","author":[{"given":"Maher K.","family":"Gandhi","sequence":"first","affiliation":[{"name":"From the Department of Medicine, University of Cambridge Clinical School, Cambridge, United Kingdom; Department of Haematology, University of Cambridge Clinical School, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark R.","family":"Wills","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Cambridge Clinical School, Cambridge, United Kingdom; Department of Haematology, University of Cambridge Clinical School, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgina","family":"Okecha","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Cambridge Clinical School, Cambridge, United Kingdom; Department of Haematology, University of Cambridge Clinical School, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth K.","family":"Day","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Cambridge Clinical School, Cambridge, United Kingdom; Department of Haematology, University of Cambridge Clinical School, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ray","family":"Hicks","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Cambridge Clinical School, Cambridge, United Kingdom; Department of Haematology, University of Cambridge Clinical School, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert E.","family":"Marcus","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Cambridge Clinical School, Cambridge, United Kingdom; Department of Haematology, University of Cambridge Clinical School, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. G. Patrick","family":"Sissons","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Cambridge Clinical School, Cambridge, United Kingdom; Department of Haematology, University of Cambridge Clinical School, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Carmichael","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Cambridge Clinical School, Cambridge, United Kingdom; Department of Haematology, University of Cambridge Clinical School, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2020021222081837100_REF1","doi-asserted-by":"crossref","unstructured":"Wills MR, Carmichael AJ, Mynard K, et al. 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