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adeno-associated virus mediated delivery of tregitope 167 ameliorates experimental colitis

World Journal of Gastroenterology 2012年第32期18卷 4288-4299页

作者： Sander van der Marel Anna Majowicz Karin Kwikkers Richard van Logtenstein Anje A te Velde Anne S De Groot Sybren L Meijer Sander J van Deventer Harald Petry Daniel W Hommes Valerie Ferreira Department of Research and Development uniQure B.V.1105 BA AmsterdamThe Netherlands Department of Gastroenterology and Hepatology Leiden University Medical Center2333 ZA LeidenThe Netherlands tytgat Institute for Liver and Intestinal Research Academic Medical CenterUniversity of Amsterdam1105 BK AmsterdamThe Netherlands EpiVax Inc. ProvidenceRI 02903United States the Institute for Immunology and Informatics University of Rhode IslandKingstonRI 02881United States Department of Pathology Academic Medical CenterUniversity of Amsterdam1105 AZ AmsterdamThe Netherlands Center for inflammatory bowel diseases UCLA Health SystemLos AngelesCA 90095United States

AIM:to explore the anti-inflammatory potential of adeno-associated virus-mediated delivery of tregitope 167 in an experimental colitis ***:the trinitrobenzene sulfonate(tNBS) model of induced colitis was used in Balb/c *** after intravenous adeno-associated virusmediated regulatory t-cell epitopes(tregitope) delivery,acute colitis was initiated by intra-rectal administration of 1.5 mg tNBS in 40% ethanol followed by a second treatment with tNBS(0.75 mg in 20% ethanol) 8 d *** groups included mice not treated with tNBS(healthy control group) and mice treated by tNBS only(diseased group).At the time of sacrifice colon weight,the disease activity index and histology damage score were *** staining of the colonic tissues was performed to asses the cellular infiltrate and the presence of transcription factor forkhead Box-P3(Foxp3).thymus,mesenteric lymph nodes,liver and spleen tissue were collected and the corresponding lymphocyte populations were further assessed by flow cytometry analysis for the expression of CD4+ t cell and regulatory t cell associated ***:the tregitope 167 treated mice gained an average of 4% over their initial body weight at the time of *** contrast,the mice treated with tNBS alone(no tregitope) developed colitis,and lost 4% of their initial body weight at the time of sacrifice(P the body weight increase that had been observed in the mice pre-treated with tregitope 167 was substantiated by a lower disease activity index and a decreased colon weight as compared to the diseased control group(P tively).Immunohistochemical staining of the colonic tissues for CD4+ showed that inflammatory cell infiltrates were present in tNBS treated mice with or without administration with tregitope 167 and that these cellular infiltrates consisted mainly of CD4+ *** both tNBS treated groups CD4+ t cell infiltrates were observed in the sub-epithelia

关键词： adeno-associated virus regulatory t cell epitope inflammatory bowel diseases adeno-associated virus

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