{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:59:51Z","timestamp":1790974791893,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2003,9,1]],"date-time":"2003-09-01T00:00:00Z","timestamp":1062374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2003,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>During acute infectious mononucleosis (AIM), large clones of Epstein\u2010Barr virus\u2010specific T lymphocytes are produced. To investigate the dynamics of clonal expansion, we measured cell proliferation during AIM using deuterated glucose to label DNA of dividing cells <jats:italic>in vivo<\/jats:italic>, analyzing cells according to CD4, CD8 and CD45 phenotype. The proportion of labeled CD8<jats:sup>+<\/jats:sup>CD45R0<jats:sup>+<\/jats:sup> T lymphocytes was dramatically increased in AIM subjects compared to controls (mean 17.5 versus 2.8%\/day; <jats:italic>p<\/jats:italic>&lt;0.005), indicating very rapid proliferation. Labeling was also increased in CD4<jats:sup>+<\/jats:sup>CD45R0<jats:sup>+<\/jats:sup> cells (7.1 versus 2.1%\/day; <jats:italic>p<\/jats:italic>&lt;0.01), but less so in CD45RA<jats:sup>+<\/jats:sup> cells. Mathematical modeling, accounting for death of labeled cells and changing pool sizes, gave estimated proliferation rates in CD8<jats:sup>+<\/jats:sup>CD45R0<jats:sup>+<\/jats:sup> cells of 11\u2013130% of cells proliferating per day (mean 47%\/day),\nequivalent to a doubling time of 1.5\u2004days and an appearance rate in blood of about 5\u00d710<jats:sup>9<\/jats:sup> cells\/day (versus 7\u00d710<jats:sup>7<\/jats:sup> cells\/day in controls). Very rapid death rates were also observed amongst labeled cells (range 28\u2013124, mean 57%\/day),indicating very short survival times in the circulation. Thus, we have shown direct evidence for massive proliferation of CD8<jats:sup>+<\/jats:sup>CD45R0<jats:sup>+<\/jats:sup> T lymphocytes in AIM and demonstrated that rapid cell division continues concurrently with greatly accelerated rates of cell disappearance.<\/jats:p>","DOI":"10.1002\/eji.200324295","type":"journal-article","created":{"date-parts":[[2003,9,23]],"date-time":"2003-09-23T22:09:06Z","timestamp":1064354946000},"page":"2655-2665","source":"Crossref","is-referenced-by-count":39,"title":["Rapid turnover of T cells in acute infectious mononucleosis"],"prefix":"10.1002","volume":"33","author":[{"given":"Derek\u2004C.","family":"Macallan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana\u2004L.","family":"Wallace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew\u2004J.","family":"Irvine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Becca","family":"Asquith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Worth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala","family":"Ghattas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George\u2004E.","family":"Griffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David\u2004F.","family":"Tough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter\u2004C.","family":"Beverley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,9]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.1.254"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.9.1499"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.10.5729"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(99)01472-3"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.9.1395"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5258.54"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/77778"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.171.3.801"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/360264a0"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8647"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200323763"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.2.708"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/4772"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.9.1277"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0896-906"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199801)28:01<22::AID-IMMU22>3.0.CO;2-7"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.10.6144"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200109280-00024"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5270.1947"},{"key":"e_1_2_7_20_2","first-page":"508","article-title":"Factors that influence activated CD8+ T cell apoptosis in patients with acute herpesvirus infections: loss of costimulatory molecules CD28, CD5 and CD6 but relative maintenance of Bax and Bcl\u2010X expression.","volume":"88","author":"Borthwick N. 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