{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:51:05Z","timestamp":1791121865535,"version":"4.1.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,12,9]]},"abstract":"<jats:p>\n                    Immunological memory, defined as more efficient immune responses on antigen reexposure, can last for decades. The current paradigm is that memory is maintained by antigen-experienced \u201cmemory T cells\u201d that can be long-lived quiescent or dividing. The contribution of T cell division to memory maintenance is poorly known and has important clinical implications. In this study, we directly addressed the role of dividing T cells in immunological memory maintenance by evaluating the consequences of their elimination. The specific ablation of dividing T cells was obtained by administration of ganciclovir to immune mice expressing the herpes simplex type 1 thymidine kinase suicide gene in T cells. We show that depletion of dividing T cells for 5 or 2 weeks suffices to abolish\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    memory responses against the male H-Y transplantation alloantigen or against lymphocytic choriomeningitis virus antigens, respectively. Similar results were obtained after the nonspecific elimination of all dividing cells by using hydroxyurea, a cytostatic toxic agent commonly used for cancer chemotherapy. This immune amnesia occurred in otherwise immunocompetent mice and despite the persistence of functional quiescent T cells displaying a \u201cmemory\u201d phenotype. Thus, division of antigen-experienced T cells is an absolute requirement for immunological memory maintenance and the current concept of memory T cells is challenged.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1936194100","type":"journal-article","created":{"date-parts":[[2003,12,9]],"date-time":"2003-12-09T13:17:48Z","timestamp":1070975868000},"page":"15017-15022","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":23,"title":["Turning immunological memory into amnesia by depletion of dividing T cells"],"prefix":"10.1073","volume":"100","author":[{"given":"Bertrand","family":"Bellier","sequence":"first","affiliation":[{"name":"Laboratoire de Biologie et Th\u00e9rapeutique des Pathologies Immunitaires, Centre National de la Recherche Scientifique-Unit\u00e9 Mixte de Recherche 7087, Universit\u00e9 Pierre et Marie Curie, 75013 Paris, France; and Institut Pasteur, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Thomas-Vaslin","sequence":"additional","affiliation":[{"name":"Laboratoire de Biologie et Th\u00e9rapeutique des Pathologies Immunitaires, Centre National de la Recherche Scientifique-Unit\u00e9 Mixte de Recherche 7087, Universit\u00e9 Pierre et Marie Curie, 75013 Paris, France; and Institut Pasteur, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Fran\u00e7oise","family":"Saron","sequence":"additional","affiliation":[{"name":"Laboratoire de Biologie et Th\u00e9rapeutique des Pathologies Immunitaires, Centre National de la Recherche Scientifique-Unit\u00e9 Mixte de Recherche 7087, Universit\u00e9 Pierre et Marie Curie, 75013 Paris, France; and Institut Pasteur, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Klatzmann","sequence":"additional","affiliation":[{"name":"Laboratoire de Biologie et Th\u00e9rapeutique des Pathologies Immunitaires, Centre National de la Recherche Scientifique-Unit\u00e9 Mixte de Recherche 7087, Universit\u00e9 Pierre et Marie Curie, 75013 Paris, France; and Institut Pasteur, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,11,21]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.16.1.201"},{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"5338","DOI":"10.4049\/jimmunol.161.10.5338","volume":"161","year":"1998","unstructured":"Oehen, S. & Brduscha-Riem, K. 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