{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:40:18Z","timestamp":1790721618528,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,4,24]],"date-time":"2002-04-24T00:00:00Z","timestamp":1019606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2002,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Recovery of total T cell numbers after <jats:italic>in vivo<\/jats:italic> T\u2010cell depletion in humans is accompanied by complex perturbation within the CD8<jats:sup>+<\/jats:sup> subset. We aimed to elucidate the reconstitution of CD8<jats:sup>+<\/jats:sup> T cells by separate analysis of putative na\u00efve CD95<jats:sup>\u2212<\/jats:sup>\u2003CD28<jats:sup>+<\/jats:sup>, memory CD95<jats:sup>+<\/jats:sup>\u2003CD28<jats:sup>+<\/jats:sup> and CD28<jats:sup>\u2212<\/jats:sup> T cell compartments after acute maximal depletion by high\u2010dose chemotherapy (HD\u2010ChT) in women with high\u2010risk breast cancer. We found that recovery of putative na\u00efve CD8<jats:sup>+<\/jats:sup>\u2003CD95<jats:sup>\u2212<\/jats:sup>\u2003CD28<jats:sup>+<\/jats:sup> and CD4<jats:sup>+<\/jats:sup>\u2003CD95<jats:sup>\u2212<\/jats:sup>\u2003CD28<jats:sup>+<\/jats:sup> T cells, was compatible with a thymus\u2010dependent regenerative pathway since their recovery was slow and time\u2010dependent, their values were tightly related to each other, and their reconstitution patterns were inversely related to age. By analysing non\u2010na\u00efve T cells, a striking diversion between putative memory T cells and CD28<jats:sup>\u2212<\/jats:sup> T cells was found. These latter increased early well beyond normal values, thus playing a pivotal role in total T\u2010cell homeostasis, and contributed to reduce the CD4\u200a:\u200aCD8 ratio. In contrast, putative memory T cells returned to values not significantly different from those seen in patients at diagnosis, indicating that this compartment may recover after HD\u2010ChT. At 3\u20135 years after treatment, na\u00efve T cells persisted at low levels, with expansion of CD28<jats:sup>\u2212<\/jats:sup> T cells, suggesting that such alterations may extend further. These findings indicate that CD28<jats:sup>\u2212<\/jats:sup> T cells were responsible for \u2018blind\u2019 T\u2010cell homeostasis, but support the notion that memory and na\u00efve T cells are regulated separately. Given their distinct dynamics, quantitative evaluation of T\u2010cell pools in patients undergoing chemotherapy should take into account separate analysis of na\u00efve, memory and CD28<jats:sup>\u2212<\/jats:sup> T cells.<\/jats:p>","DOI":"10.1046\/j.1365-2567.2002.01400.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T02:31:01Z","timestamp":1047436261000},"page":"27-37","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["T\u2010cell dynamics after high\u2010dose chemotherapy in adults: elucidation of the elusive CD8<sup>+<\/sup> subset reveals multiple homeostatic T\u2010cell compartments with distinct implications for immune competence"],"prefix":"10.1111","volume":"106","author":[{"given":"Francesco F.","family":"Fagnoni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Lozza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Zibera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Zambelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Ponchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Gibelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Oliviero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Pavesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Gennari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Vescovini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Sansoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianantonio","family":"Da Prada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gioacchino","family":"Robustelli Della Cuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,4,24]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/46218"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(98)01344-9"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0795-674"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1295-1279"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6363702"},{"key":"e_1_2_6_7_2","doi-asserted-by":"crossref","first-page":"4609","DOI":"10.4049\/jimmunol.156.12.4609","article-title":"Thymic\u2010independent T cell regeneration occurs via antigen\u2010driven expansion of peripheral T cells resulting in a repertoire that is limited in diversity and prone to skewing","volume":"156","author":"Mackall CL","year":"1996","journal-title":"J Immunol"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.10.2983"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.11.3380"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1700624"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.5.1471"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199501193320303"},{"key":"e_1_2_6_13_2","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1182\/blood.V90.2.850","article-title":"Essential role of the thymus to reconstitute na\u00efve (CD45RA+) T\u2010helper cells after human allogeneic bone marrow transplantation","volume":"90","author":"Heitger A","year":"1997","journal-title":"Blood"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02293-5"},{"key":"e_1_2_6_15_2","doi-asserted-by":"crossref","first-page":"2860","DOI":"10.1182\/blood.V95.9.2860.009k35_2860_2868","article-title":"Shortage of circulating na\u00efve CD8 (+) T cells provides new insights on immunodeficiency in aging","volume":"95","author":"Fagnoni FF","year":"2000","journal-title":"Blood"},{"key":"e_1_2_6_16_2","first-page":"924","article-title":"Efficacy of epirubicin\/paclitaxel combination in mobilizing large amounts of hematopoietic progenitor cells in patients with metastatic breast cancer showing optimal response to the same chemotherapy regimen","volume":"84","author":"Zibera C","year":"1999","journal-title":"Haematologica"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0320(20011001)45:2<124::AID-CYTO1154>3.3.CO;2-C"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/84701"},{"key":"e_1_2_6_19_2","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.4049\/jimmunol.150.4.1147","article-title":"CD28\u2212 T lymphocytes. Antigenic and functional properties","volume":"150","author":"Azuma M","year":"1993","journal-title":"J Immunol"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1996.d01-689.x"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.2.609"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.9.3789"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.10.3700"},{"key":"e_1_2_6_24_2","doi-asserted-by":"crossref","first-page":"3662","DOI":"10.1182\/blood.V90.9.3662","article-title":"Long\u2010term depletion of na\u00efve T cells in patients treated for Hodgkin's disease","volume":"90","author":"Watanabe N","year":"1997","journal-title":"Blood"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI195"},{"key":"e_1_2_6_26_2","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1128\/jvi.70.3.2022-2026.1996","article-title":"Predominant involvement of CD8+CD28\u2212 lymphocytes in human immunodeficiency virus\u2010specific cytotoxic activity","volume":"70","author":"Fiorentino S","year":"1996","journal-title":"J Virol"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/79667"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1058867"},{"key":"e_1_2_6_29_2","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.4049\/jimmunol.151.4.2237","article-title":"Tissue\u2010specific distribution and age\u2010dependent increase of human CD11b+ T cells","volume":"151","author":"Hoshino T","year":"1993","journal-title":"J Immunol"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/44385"},{"key":"e_1_2_6_31_2","doi-asserted-by":"crossref","first-page":"3327","DOI":"10.4049\/jimmunol.162.6.3327","article-title":"Postthymic development of CD28\u2013CD8+ T cell subset: age\u2010associated expansion and shift from memory to na\u00efve phenotype","volume":"162","author":"Nociari MM","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(99)80026-0"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5466.675"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(99)00068-6"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/25374"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/79549"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02284-4"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0196-52"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1179\/joc.2001.13.1.15"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1365-2567.2002.01400.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1046\/j.1365-2567.2002.01400.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T03:17:41Z","timestamp":1695871061000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1046\/j.1365-2567.2002.01400.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,4,24]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2002,5]]}},"alternative-id":["10.1046\/j.1365-2567.2002.01400.x"],"URL":"https:\/\/doi.org\/10.1046\/j.1365-2567.2002.01400.x","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,4,24]]},"assertion":[{"value":"2002-04-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}