{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:40:05Z","timestamp":1789188005489,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,2,20]],"date-time":"2012-02-20T00:00:00Z","timestamp":1329696000000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Gene transfer in the thymus, based on HIV\u2010derived lentiviral vectors, is a promising avenue for modulation of T cell selection and autoimmunity. However, the impact of intrathymic (IT) injections on an antigen\u2010specific immune response elicited in the periphery of normal mice has not been investigated yet.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Highly concentrated stocks of lentiviral vectors expressing the soluble form of hemaglutinin of the influenza virus (LvHA) were injected in the thymus of normal BALB\/c mice. The CD4 and CD8\u2010mediated immune responses to HA after peripheral immunization were measured by various parameters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We first show that a lentiviral vector expressing the luciferase was detected for at least 2\u2009months after IT\u2010injections. We then show that the LvHA vector could elicit a functional CD4\u2010 and CD8\u2010T cell\u2010mediated immune responses in the peripheral lymphoid organs of BALB\/c mice. IT\u2010injection of the LvHA vector significantly curbed this response: lower numbers of transferred HA\u2010specific CD4<jats:sup>+<\/jats:sup> T cells were found in LvHA\u2010injected compared to control animals. Furthermore, lower frequencies of HA\u2010specific CD8<jats:sup>+<\/jats:sup> T cells, interferon \u03b3\u2010producing cells and cytotoxic cells were detected from 3\u2009weeks to 3\u2009months in LvHA\u2010injected mice compared to controls. However, these reduced CD8\u2010mediated responses were not increased after depletion of CD25<jats:sup>+<\/jats:sup> cells <jats:italic>in vitro<\/jats:italic> or <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results obtained in the present study show that injection of the LvHA lentiviral vector significantly curtailed the immune response to the same antigen in the periphery. Increased selection of HA\u2010specific regulatory T cells and negative selection of HA\u2010specific CD8<jats:sup>+<\/jats:sup> T cell precursors may explain the results. Our work establish the feasibility of IT\u2010injections of lentiviral vectors to manipulate T cell tolerance in the thymus of normal mice, for basic and pre\u2010clinical research. Copyright \u00a9 2012 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.1650","type":"journal-article","created":{"date-parts":[[2012,1,7]],"date-time":"2012-01-07T17:26:35Z","timestamp":1325957195000},"page":"90-99","source":"Crossref","is-referenced-by-count":11,"title":["Intrathymic injection of lentiviral vector curtails the immune response in the periphery of normal mice"],"prefix":"10.1002","volume":"14","author":[{"given":"Ga\u00eblle","family":"Gottrand","sequence":"first","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie UPMC University of Paris 06  Paris France"},{"name":"Centre National de la Recherche Scientifique CNRS, UMR 7211  Paris France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, INSERM, U959  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kahina","family":"Taleb","sequence":"additional","affiliation":[{"name":"CNRS UMR 8104, INSERM U1016 Institut Cochin  Paris 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