{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T13:08:38Z","timestamp":1792242518224,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,2,23]],"date-time":"2012-02-23T00:00:00Z","timestamp":1329955200000},"content-version":"vor","delay-in-days":53,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:p>Kemter E, Lieke T, Kessler B, Kurome M, Wuensch A, Summerfield A, Ayares D, Nagashima H, Baars W, Schwinzer R, Wolf E. Human TNF\u2010related apoptosis\u2010inducing ligand\u2010expressing dendritic cells from transgenic pigs attenuate human xenogeneic T cell responses. Xenotransplantation 2012; 19: 40\u201351. \u00a9 2012 John Wiley &amp; Sons A\/S.<\/jats:p><jats:p><jats:bold>Abstract:\u2002<\/jats:bold><jats:bold> Background:\u2002<\/jats:bold> Efficient and precise techniques for the genetic modification of pigs facilitate the generation of tailored donor animals for xenotransplantation. Numerous transgenic pig lines exist with the focus on inhibition of the complement system and of humoral immune responses. In addition, immune cell\u2010based responses need to be controlled to prevent pig\u2010to\u2010primate xenograft rejection. Expression of human (hu) TNF\u2010related apoptosis\u2010inducing ligand (TRAIL) on porcine cells has the potential to ameliorate human T cell responses.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> We generated transgenic pigs expressing human tumor necrosis factor (TNF)\u2010related apoptosis\u2010inducing ligand (huTRAIL) under the control of either the mouse H2K<jats:sup>b<\/jats:sup> promoter or a CMV enhancer\/chicken \u03b2\u2010actin (CAG) promoter, the latter one (CAG\u2010huTRAIL) on a <jats:italic>GGTA1<\/jats:italic> knockout\/huCD46 transgenic background. The biological activity of huTRAIL was demonstrated by its apoptosis\u2010inducing effect on Jurkat lymphoma cells. To clarify whether huTRAIL affects also primary immune cells and whether its effects depend on the presence of co\u2010stimulatory molecules, we exposed human peripheral blood mononuclear cells (PBMC) or isolated T cells to huTRAIL\u2010expressing porcine fibroblasts or dendritic cells in vitro.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> H2K<jats:sup>b<\/jats:sup>\u2010huTRAIL transgenic pigs express huTRAIL mainly in the spleen and secondary lymphoid tissues. The CAG\u2010huTRAIL construct facilitated huTRAIL expression in multiple organs, the level being at least one order of magnitude higher than in H2K<jats:sup>b<\/jats:sup>\u2010huTRAIL transgenic pigs. Incubation with huTRAIL\u2010expressing H2K<jats:sup>b<\/jats:sup>\u2010huTRAIL transgenic porcine dendritic cells decreased human T cell proliferation significantly without any signs of apoptosis. In spite of the high transgene expression level, CAG\u2010huTRAIL transgenic fibroblasts did not affect proliferation of human PBMC, independent of their activation state.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> These results suggest huTRAIL expression on porcine dendritic cells as a possible strategy to attenuate T cell responses against pig\u2010to\u2010primate xenografts.<\/jats:p>","DOI":"10.1111\/j.1399-3089.2011.00688.x","type":"journal-article","created":{"date-parts":[[2012,2,24]],"date-time":"2012-02-24T02:10:44Z","timestamp":1330049444000},"page":"40-51","source":"Crossref","is-referenced-by-count":20,"title":["Human TNF\u2010related apoptosis\u2010inducing ligand\u2010expressing dendritic cells from transgenic pigs attenuate human xenogeneic T cell responses"],"prefix":"10.1111","volume":"19","author":[{"given":"Elisabeth","family":"Kemter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Lieke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Kessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayuko","family":"Kurome","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annegret","family":"Wuensch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"Summerfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ayares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nagashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiebke","family":"Baars","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Schwinzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eckhard","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,2,23]]},"reference":[{"key":"e_1_2_8_2_2","first-page":"217","article-title":"The pig as a xenograft donor","volume":"42","author":"Sachs DH","year":"1994","journal-title":"Pathol Biol (Paris)"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3089.2003.02092.x"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0995-869"},{"key":"e_1_2_8_5_2","first-page":"51","article-title":"The role of skin bank in the treatment of severely burnt patients","volume":"46","author":"Dvorankova B","year":"2004","journal-title":"Acta Chir Plast"},{"key":"e_1_2_8_6_2","first-page":"395","article-title":"Pig skin over open wounds","volume":"149","author":"Habal MB","year":"1979","journal-title":"Surg Gynecol Obstet"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-010-0610-9"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1068228"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1078942"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.21127"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1171"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2009.02850.x"},{"key":"e_1_2_8_13_2","doi-asserted-by":"crossref","first-page":"5249","DOI":"10.4049\/jimmunol.155.11.5249","article-title":"Human anti\u2010porcine xenogeneic T cell response. 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