{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T08:19:18Z","timestamp":1743063558993},"reference-count":58,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2005,12,7]],"date-time":"2005-12-07T00:00:00Z","timestamp":1133913600000},"content-version":"vor","delay-in-days":4542,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[1993,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We report that targeting of T cell receptors (TcR) to non\u2010major histocompatibility complex (MHC) molecules on thymic cortical epithelial cells by hybrid antibodies <jats:italic>in vivo<\/jats:italic> and in fetal thymic organ cultures results in phenotypic and functional differentiation of thymocytes. A single pulse with hybrid antibodies rescues immature, CD4\/8 double\u2010positive thymocytes from their programmed death <jats:italic>in vivo<\/jats:italic>, induces expression of the early activation antigen CD69 followed by TcR up\u2010regulation, concomitant down\u2010regulation of CD8 or CD4 and their conversion to functional mature T cells by day 3. This temporal sequence of maturation only affects small thymocytes without co\u2010induction of blastogenesis. TcR targeting to MHC class II\u2010positive epithelial cells predominantly induces CD4\u2010positive T cells. This generation of CD4 single\u2010positive T cells occurs also in MHC class II\u2010deficient mice and thus is independent of CD4\u2010MHC class II interactions. Moreover, in the presence of a specific deleting antigen (Mls 1<jats:sup>a<\/jats:sup>),TcR targeting results in transient activation of immature thymocytes, however, not in subsequent TcR (V\u03b26) up\u2010regulation and development of single\u2010positive T cells. Our findings imply that TcR cross\u2010linking to cortical epithelial cells is sufficient to confer a differentiation signal to immature thymocytes. Futhermore, this approach distinguishes two independent TcR\u2010mediated intrathymic events: activation and subsequent deletion of the same thymocyte subset.<\/jats:p>","DOI":"10.1002\/eji.1830230740","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T19:03:53Z","timestamp":1172775833000},"page":"1661-1670","source":"Crossref","is-referenced-by-count":32,"title":["T cell receptor targeting to thymic cortical epithelial cells <i>in vivo<\/i> induces survival, activation and differentiation of immature thymocytes"],"prefix":"10.1002","volume":"23","author":[{"given":"Klaus\u2010Peter","family":"M\u00fcller","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno A.","family":"Kyewski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,12,7]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90044-5"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1972592"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.08.040190.002531"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(91)90162-M"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.09.040191.003111"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90501-1"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90502-3"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/359729a0"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.176.3.845"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/4.6.707"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/359330a0"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1694041"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(90)90141-U"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2125367"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/351482a0"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830230315"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/351150a0"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90980-X"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.172.3.835"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/346861a0"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(81)90016-7"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/337181a0"},{"key":"e_1_2_1_24_2","first-page":"65","volume":"173","author":"Kyewski B.","year":"1991","journal-title":"Curr. 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