{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T06:46:09Z","timestamp":1768891569975,"version":"3.49.0"},"reference-count":3,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2002,1,1]],"date-time":"2002-01-01T00:00:00Z","timestamp":1009843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2002,1,1]],"date-time":"2002-01-01T00:00:00Z","timestamp":1009843200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathobiology"],"published-print":{"date-parts":[[2002]]},"abstract":"<jats:p>&lt;i&gt;Objective:&lt;\/i&gt; The proinflammatory cytokine interleukin (IL)-6 is involved in various chronic inflammatory processes. IL-6 is a predominant cytokine produced by lamina propria T cells in Crohn\u2019s disease and experimental colitis. This study was designed to examine the effect of a neutralizing IL-6-receptor (IL-6R) antibody on the programmed cell death of mucosal T cells in the CD62L+ CD4+ SCID transfer model of chronic experimental colitis in mice and to gain more insight into the pathogenesis of this transfer colitis model. &lt;i&gt;Methods:&lt;\/i&gt; For adoptive transfer, we isolated CD62L+ CD4+ double-positive T cells from wild-type BALB\/c mice followed by intraperitoneal application of 1 million cells in CB17 SCID mice. The purity of the transferred T-cell population was tested by FACS analysis. Cytokine secretion was measured by ELISA. Western blot analysis was performed to detect phospho-STAT-3 in protein extracts of splenic cells. Cryo- and paraffin colon cross-sections were used to perform immunochemical or fluorescence TUNEL stainings. &lt;i&gt;Results:&lt;\/i&gt; We isolated CD62L+ CD4+ and CD62L\u2013 CD4+ T cells. In vitro studies showed an increased production of IL-4 by CD62L\u2013 CD4+ T cells compared to CD62L+ T cells. 8\u201310 weeks after transfer of CD62L+ CD4+ T cells in SCID mice, reconstituted mice developed wasting disease, anal prolapse and diarrhea, whereas mice reconstituted with CD62L\u2013 CD4+ did not, similar to anti-IL-6R-treated CD62L+ CD4+-reconstituted SCID mice. Anti-IL-6R-treated reconstituted SCID mice showed decreased levels of activated STAT-3. The previously described efficacy of anti-IL-6R antibody treatment on colitis activity appeared to be due to the induction of apoptosis, as many TUNEL-positive cells were detected in the lamina propria. &lt;i&gt;Conclusions:&lt;\/i&gt; These results suggest that the activation of the IL-6\/STAT-3-signaling pathway plays a pivotal role in the pathogenesis of CD62L+ CD4+ transfer colitis. Moreover, the application of a neutralizing antibody to IL-6R induces apoptosis in transferred T cells. These data implicate the importance of anti-apoptotic pathways in chronic disease and might contribute to future therapies.<\/jats:p>","DOI":"10.1159\/000068150","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T21:05:40Z","timestamp":1050440740000},"page":"170-176","source":"Crossref","is-referenced-by-count":50,"title":["A New Model of Chronic Colitis in SCID Mice Induced by Adoptive Transfer of CD62L+ CD4+ T Cells: Insights into the Regulatory Role of Interleukin-6 on Apoptosis"],"prefix":"10.1159","volume":"70","author":[{"given":"Jonas","family":"Mudter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Wirtz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter R.","family":"Galle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus F.","family":"Neurath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2003,2,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(99)00032-1"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/75068"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1995.1085"}],"container-title":["Pathobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/68150","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/68150","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T03:30:34Z","timestamp":1745465434000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000068150"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002]]},"references-count":3,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2003,2,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000068150","archive":["Portico"],"relation":{},"ISSN":["1015-2008","1423-0291"],"issn-type":[{"value":"1015-2008","type":"print"},{"value":"1423-0291","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002]]}}}