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- Title
Successful immunotherapy of autoimmune cholangitis by adoptive transfer of forkhead box protein 3<sup>+</sup> regulatory T cells.
- Authors
Tanaka, H.; Zhang, W.; Yang, G.‐X.; Ando, Y.; Tomiyama, T.; Tsuneyama, K.; Leung, P.; Coppel, R. L.; Ansari, A. A.; Lian, Z. X.; Ridgway, W. M.; Joh, T.; Gershwin, M. E.
- Abstract
Treatment of primary biliary cirrhosis ( PBC) has lagged behind that of other autoimmune diseases. In this study we have addressed the potential utility of immunotherapy using regulatory T cells ( Treg) to treat murine autoimmune cholangitis. In particular, we have taken advantage of our ability to produce portal inflammation and bile duct cell loss by transfer of CD8+ T cells from the dominant negative form of transforming growth factor beta receptor type II ( dnTGF-β RII) mice to recombination-activating gene ( Rag)1-/- recipients. We then used this robust established adoptive transfer system and co-transferred CD8+ T cells from dnTGF-β RII mice with either C57 BL/6 or dnTGF-β RII forkhead box protein 3 ( FoxP3+) T cells. Recipient mice were monitored for histology, including portal inflammation and intralobular biliary cell damage, and also included a study of the phenotypical changes in recipient lymphoid populations and local and systemic cytokine production. Importantly, we report herein that adoptive transfer of Treg from C57 BL/6 but not dnTGF-β RII mice significantly reduced the pathology of autoimmune cholangitis, including decreased portal inflammation and bile duct damage as well as down-regulation of the secondary inflammatory response. Further, to define the mechanism of action that explains the differential ability of C57 BL/6 Treg versus dnTGF-β RII Treg on the ability to down-regulate autoimmune cholangitis, we noted significant differential expression of glycoprotein A repetitions predominant (GA RP), CD73, CD101 and CD103 and a functionally significant increase in interleukin ( IL)-10 in Treg from C57 BL/6 compared to dnTGF-β RII mice. Our data reflect the therapeutic potential of wild-type CD4+ FoxP3+ Treg in reducing the excessive T cell responses of autoimmune cholangitis, which has significance for the potential immunotherapy of PBC.
- Subjects
TREATMENT of cirrhosis of the liver; AUTOIMMUNE diseases; CHOLANGITIS; IMMUNOTHERAPY; FORKHEAD transcription factors; T cells; GENETIC regulation; PHYSIOLOGY
- Publication
Clinical & Experimental Immunology, 2014, Vol 178, Issue 2, p253
- ISSN
0009-9104
- Publication type
Article
- DOI
10.1111/cei.12415