Hepatocyte immunology and transplantation: current status and future potential

Purpose of review The purpose of this review is to highlight our current understanding of hepatocyte immunobiology derived from both experimental and clinical studies and to discuss the implications of these findings in the context of hepatocyte transplantation. Recent findings Hepatocytes express, upregulate, and produce many immunologically active molecules including MHC and conventional costimulation molecules known to be important in T-cell activation. In addition, recent studies highlight hepatocyte expression and upregulation of adhesion molecules (ICAM-1, VAP-1, E-cadherin, LI-cadherin) important in leukocyte recruitment and adhesion; they may also provide costimulation signals which activate T cells. Hepatocytes also produce cytokines, chemokines, and anaphylatoxins, and express receptors that promote interactions with the innate and adaptive immune systems. Under conditions of ischemia and liver inflammation, the constitutive expression of ASGP-R and Fas may target transplanted hepatocytes for immune destruction. Studies from our laboratory have addressed CD4- and CD8-dependent immune pathways activated by allogeneic hepatocytes. Although the latter pathway is resistant to conventional immunosuppression, a short-term strategy targeting LFA-1 and CD40L effectively prevents CD8-dependent rejection and achieves long-term hepatocellular allograft survival in a functional murine model of hepatocyte transplantation. Finally, the immune consequences of the extracellular milieu where hepatocytes are transplanted have recently been appreciated. Summary This review presents evidence from clinical and experimental studies, which underscore the potent immunogenicity of liver parenchymal cells and highlights areas of future progress in hepatocyte immunology. This may enhance hepatocyte transplantation as a therapeutic modality for patients with liver disease.