However, PD1 is silenced in CD8+ T cells of aged Ae2a,b−/− mice and this event, together with derangement of other immunosuppressive mechanisms, allows for vigorous expansion of intrahepatic CD8+ T cells and autoimmune cholangitis (Figure 11) Our findings emphasize the relevance of AE2 abnormalities and age-related changes in the expression of immunoregulatory molecules for the development of autoimmune liver disease. This evidence concerns the gene CD8A and autoimmune hepatitis.