{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T05:48:05Z","timestamp":1761630485104},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2008,5,8]],"date-time":"2008-05-08T00:00:00Z","timestamp":1210204800000},"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":[[2008,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Regulatory T cells (Treg) have been shown to play a role in the prevention of autoimmune diseases and transplant rejection. Based on an established protocol known to generate alloantigen reactive Treg <jats:italic>in vivo<\/jats:italic>, we have developed a strategy for the <jats:italic>in vitro<\/jats:italic> selection of Treg. Stimulation of unfractionated CD4<jats:sup>+<\/jats:sup> T cells from naive CBA.Ca (H2<jats:sup>k<\/jats:sup>) mice with C57BL\/10 (H2<jats:sup>b<\/jats:sup>) splenocytes in the presence of an anti\u2010CD4 antibody, YTS 177, resulted in the selection of Treg able to inhibit proliferation of naive T cells. <jats:italic>In vivo<\/jats:italic>, the cells were able to prevent rejection of 80% C57BL\/10 skin grafts when co\u2010transferred to CBA.Rag<jats:sup>\u2013\/\u2013<\/jats:sup> mice together with naive CD45RB<jats:sup>high<\/jats:sup>CD4<jats:sup>+<\/jats:sup> cells. Purification of CD62L<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> cells from the cultures enriched for cells with regulatory activity; as now 100% survival of C57BL\/10 skin grafts was achieved. Furthermore, differentiation of Treg could be also achieved when using purified CD25<jats:sup>\u2013<\/jats:sup>CD4<jats:sup>+<\/jats:sup> naive T cells as a starting population. Interestingly, further <jats:italic>in vitro<\/jats:italic> expansion resulted in a partial loss of CD4<jats:sup>+<\/jats:sup> cells expressing both CD62L and CD25 and abrogation of their regulatory activity <jats:italic>in vivo<\/jats:italic>. This study shows that alloantigen stimulation in the presence of anti\u2010CD4 <jats:italic>in vitro<\/jats:italic> provides a simple and effective strategy to generate alloreactive Treg.<\/jats:p>","DOI":"10.1002\/eji.200737562","type":"journal-article","created":{"date-parts":[[2008,5,8]],"date-time":"2008-05-08T15:32:05Z","timestamp":1210260725000},"page":"1677-1688","source":"Crossref","is-referenced-by-count":21,"title":["Anti\u2010CD4\u2010mediated selection of Treg <i>in vitro<\/i> \u2013 <i>in vitro<\/i> suppression does not predict <i>in vivo<\/i> capacity to prevent graft rejection"],"prefix":"10.1002","volume":"38","author":[{"given":"Vanessa","family":"Oliveira","sequence":"first","affiliation":[]},{"given":"Birgit","family":"Sawitzki","sequence":"additional","affiliation":[]},{"given":"Stephanie","family":"Chapman","sequence":"additional","affiliation":[]},{"given":"Christine","family":"Appelt","sequence":"additional","affiliation":[]},{"given":"Inga","family":"Gebuhr","sequence":"additional","affiliation":[]},{"given":"Joanna","family":"Wieckiewicz","sequence":"additional","affiliation":[]},{"given":"Elaine","family":"Long","sequence":"additional","affiliation":[]},{"given":"Kathryn\u2004J.","family":"Wood","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2008,5,20]]},"reference":[{"key":"e_1_2_8_1_2","doi-asserted-by":"crossref","first-page":"5317","DOI":"10.4049\/jimmunol.162.9.5317","article-title":"Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self\u2010tolerance.","volume":"162","author":"Itoh M.","year":"1999","journal-title":"J. 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