Regulatory T Cells in Autoimmune and Viral Chronic Hepatitis

Figure 1

Role of CD4⁺ Tregs in the pathogenesis of autoimmune hepatitis. Based on data from experimental models and clinical observation we propose the following sequence of events leading to AIH through molecular mimicry. When an efficient peripheral tolerance to liver-expressed autoantigens (red) is induced either by preexisting natural Tregs or through the peripheral conversion of naïve CD4⁺ T cells to CD4⁺ Tregs (green), activation of autoreactive CD4⁺ T cells (yellow) would be abrogated and development of AIH prevented (1). However, when CD4⁺ Tregs are present in small numbers, activation through molecular mimicry of autoreactive CD4⁺ T cells against an antigen mimic (red/green) could occur leading to the activation of autoreactive B cells (pink) and production of autoantibodies (2). Autoreactive CD4⁺ T cells could then go on to induce an autoreactive CD8⁺ cytotoxic T cell response (blue) to liver-expressed autoantigens leading to hepatocyte lysis, release of autoantigens (red), and perpetuation of the T and B cell autoimmune response to the liver.