Mechanisms of T cell death in the liver: to Bim or not to Bim?

Abstract

Despite being a non-lymphoid organ, the liver displays immunological properties distinct from other solid organs and is associated with the induction of T cell tolerance. This property has been demonstrated in several clinical settings including transplantation and hepatotropic viral infections, such as those induced by hepatitis B and C viruses. Many models have been proposed to explain the 'liver tolerance effect', but the molecular and cellular mechanism(s) mediating this phenomenon remain unknown. Using transgenic mouse models, we have previously shown that the liver is the only non-lymphoid organ able to retain and activate naïve CD8+ T cells independently of lymphoid tissues in an antigen-specific manner. These findings, confirmed by other groups, have opened new possibilities to explain the remarkable capacity of the liver to induce antigen-specific tolerance in transplantation and following infection by hepatotropic viruses, such as the hepatitis C and B viruses. In our models, T cells activated by hepatocytes that proliferate die by neglect in a Bim-dependent manner. This paper will thus review the evidence showing Bim playing a critical role following intrahepatic primary T cell activation.