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 ex vivo expanded CXCR31 Tregs in mice with AIH efficiently targeted the inflamed liver, restored peripheral tolerance to FTCD, and induced remission of AIH. Conclusion: Peripheral tolerance to liver autoantigens in AIH is paramount. Autologous infusion of ex vivo expanded CXCR31 Tregs in AIH patients could be an effective therapeutic approach to restore peripheral tolerance and induce remission of AIH. (HEPATOLOGY 2013;57:217-227)
We report that low dose αCD3 antibody administration is an effective treatment for AIH in an experimental model of type 2 AIH. These data suggest that αCD3 antibody therapy could be tested in clinical trials as a rescue therapy for patients with uncontrolled AIH.
Restrictions on boys’ capacities to process and to show emotion, however detrimental for their development, constitutes a key lesson of the masculinity curriculum learned in schools. To explore what schools can do to offer support for boys’ resistance to this curriculum, a series of studies has been conducted at a suburban independent school outside Philadelphia, PA. The present study uses a mixed-method design, including teachers, university-based researchers and students on the research team, to examine how boys’ participation in a peer counseling program influenced their sense of self and self-expression. A survey, focus groups, interviews, and observations supported the usefulness of the intervention for boys. The following qualitative themes emerged: (1) The constraining effect of the school’s masculinity culture on boys’ emotional development; (2) the value of a “safe space” in overcoming this culture and in promoting boys’ learning and connection; (3) boys’ ready development of new skills, especially in relation to emotional experiences, when invited to do so; (4) the deepening and broadening of boys’ friendships resulting from their self-disclosure and mutual support.
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