{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T02:50:34Z","timestamp":1771469434411,"version":"3.50.1"},"reference-count":36,"publisher":"Proceedings of the National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,4,12]]},"abstract":"<jats:p>Cytokine immunotherapies targeting T lymphocytes are attractive clinical interventions against viruses and tumors. In the mouse, the homeostasis of memory \u03b1\/\u03b2 CD8<jats:sup>+<\/jats:sup>T cells and natural killer (NK) cells is significantly improved with increased IL-15 bioavailability. In contrast, the role of \u201ctranspresented\u201d IL-15 on human T-cell development and homeostasis in vivo is unknown. We found that both CD8 and CD4 T cells in human immune system (HIS) mice are highly sensitive to transpresented IL-15 in vivo, with both na\u00efve (CD62L<jats:sup>+<\/jats:sup>CD45RA<jats:sup>+<\/jats:sup>) and memory phenotype (CD62L<jats:sup>\u2212<\/jats:sup>CD45RO<jats:sup>+<\/jats:sup>) subsets being significantly increased following IL-15 \u201cboosting.\u201d The unexpected global improvement in human T-cell homeostasis involved enhanced proliferation and survival of both na\u00efve and memory phenotype peripheral T cells, which potentiated B-cell responses by increasing the frequency of antigen-specific responses following immunization. Transpresented IL-15 did not modify T-cell activation patterns or alter the global T-cell receptor (TCR) repertoire diversity. Our results indicate an unexpected effect of IL-15 on human T cells in vivo, in particular on CD4<jats:sup>+<\/jats:sup>T cells. As IL-15 promotes human peripheral T-cell homeostasis and increases the frequency of neutralizing antibody responses in HIS mice, IL-15 immunotherapy could be envisaged as a unique approach to improve vaccine responses in the clinical setting.<\/jats:p>","DOI":"10.1073\/pnas.1019167108","type":"journal-article","created":{"date-parts":[[2011,3,29]],"date-time":"2011-03-29T02:34:26Z","timestamp":1301366066000},"page":"6217-6222","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":72,"title":["IL-15 transpresentation promotes both human T-cell reconstitution and T-cell\u2013dependent antibody responses in vivo"],"prefix":"10.1073","volume":"108","author":[{"given":"Nicholas D.","family":"Huntington","sequence":"first","affiliation":[{"name":"Innate Immunity Unit, Immunology Department, Institut Pasteur, 75724 Paris, France;"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U668, 75724 Paris, France;"},{"name":"Part of the Human Vaccine Consortium, \u201cGrand Challenges in Global Health #4: devise reliable testing systems for new vaccines\u201d ();"}]},{"given":"Nuno L.","family":"Alves","sequence":"additional","affiliation":[{"name":"Innate Immunity Unit, Immunology Department, Institut Pasteur, 75724 Paris, France;"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U668, 75724 Paris, France;"}]},{"given":"Nicolas","family":"Legrand","sequence":"additional","affiliation":[{"name":"Part of the Human Vaccine Consortium, \u201cGrand Challenges in Global Health #4: devise reliable testing systems for new vaccines\u201d ();"},{"name":"Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105, Amsterdam, The Netherlands;"}]},{"given":"Annick","family":"Lim","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U668, 75724 Paris, France;"},{"name":"Lymphocyte Development Unit, Institut Pasteur, 75724 Paris, France;"}]},{"given":"Helene","family":"Strick-Marchand","sequence":"additional","affiliation":[{"name":"Innate Immunity Unit, Immunology Department, Institut Pasteur, 75724 Paris, France;"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U668, 75724 Paris, France;"},{"name":"Part of the Human Vaccine Consortium, \u201cGrand Challenges in Global Health #4: devise reliable testing systems for new vaccines\u201d ();"}]},{"given":"Jean-Jacques","family":"Mention","sequence":"additional","affiliation":[{"name":"Innate Immunity Unit, Immunology Department, Institut Pasteur, 75724 Paris, France;"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U668, 75724 Paris, France;"},{"name":"Part of the Human Vaccine Consortium, \u201cGrand Challenges in Global Health #4: devise reliable testing systems for new vaccines\u201d 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testing systems for new vaccines\u201d ();"},{"name":"Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, D-38124 Braunschweig, Germany;"}]},{"given":"Carlos","family":"Guzman","sequence":"additional","affiliation":[{"name":"Part of the Human Vaccine Consortium, \u201cGrand Challenges in Global Health #4: devise reliable testing systems for new vaccines\u201d ();"},{"name":"Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, D-38124 Braunschweig, Germany;"}]},{"given":"Patrick","family":"Soussan","sequence":"additional","affiliation":[{"name":"INSERM U845, Centre de Recherche Croissance et Signalisation, Universit\u00e9 Paris Descartes, H\u00f4pital Necker Enfants Malades, 75015 Paris, France;"},{"name":"INSERM Laboratoire de Virologie, H\u00f4pital Tenon, Assistance Publique-Hopitaux de Paris, 75020 Paris, 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