Adoptive transfer of ex vivo expanded regulatory T cells in an autoimmune hepatitis murine model restores peripheral tolerance1. Issue 1 (1st October 2012)

• Record Type: Journal Article
• Authors: Lapierre, Pascal; Béland, Kathie; Yang, Roland; Alvarez, Fernando
• Is Part Of: Hepatology. Volume 57:Issue 1(2013:Jan.)
• Page Start: 217
• Page End: 227
• Publication Date: 2012-10-01
• Subjects: Heart -- Diseases -- Nursing -- Periodicals; Lungs -- Diseases -- Nursing -- Periodicals; Intensive care nursing -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1002/hep.26023
• Languages: English
• ISSNs: 0270-9139

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Autoimmune hepatitis (AIH) is characterized by a loss of immunological tolerance to hepatocytes. Patients respond well to immunosuppression but progression to endstage liver disease occurs in 10%‐20% of cases, leading to liver transplantation. Using a murine model of type 2 AIH, we identified susceptibility factors for autoimmune hepatitis and attempted to restore immunological tolerance to liver autoantigens. An increased ectopic expression of a liver autoantigen (FTCD) in the thymus leading to reduced numbers of circulating autoreactive T cells was sufficient to prevent development of AIH in mice. However, in the presence of a reduced central tolerance to FTCD, a strong regulatory T‐cell response was able to inhibit proliferation of liver‐specific autoreactive T cells and prevent AIH. Development of a severe AIH stemmed from reduced numbers of functional regulatory T cell (Tregs) leading to an increased proliferation of FTCD‐specific autoreactive T and B cells. Adoptive transfer of <italic>ex vivo</italic> expanded CXCR3<sup>+</sup> Tregs in mice with AIH efficiently targeted the inflamed liver, restored peripheral tolerance to FTCD, and induced remission of AIH. <italic>Conclusion</italic>: Peripheral tolerance to liver autoantigens in AIH is paramount. Autologous infusion of <italic>ex vivo</italic> expanded CXCR3<sup>+</sup> Tregs in AIH patients could be an effective therapeutic approach to restore peripheral tolerance and induce remission of AIH. (H<sc>EPATOLOGY</sc> 2013)</p> </abstract>