Apoptosis as a mechanism of tissue injury in liver allograft rejection.

Recent studies suggest that apoptosis is an important mechanism of cell death in the rejection of liver allografts and that infiltrating host lymphocytes mediate this process. The first section of this chapter addresses the cells and molecules that initiate the immune response following transplantation of a liver allograft. The recognition of donor alloantigens by infiltrating host lymphocytes stimulates a cascade of immune events which culminate in development of the effector cells that mediate tissue damage. Studies which demonstrate that apoptosis of hepatocytes and bile duct cells accompany allograft rejection are detailed in the second section of this chapter. The final section discusses the potential pathways which lead to apoptosis in liver allograft rejection. The contributions of the granule-exocytosis pathway, the Fas-mediated pathway, and cytokines to the induction of apoptosis in liver allografts are discussed. In addition, the concept that alloreactive graft infiltrating cells are deleted by apoptosis is presented. A further understanding of the mechanisms involved in apoptosis will lead to unique approaches toward the goal of achieving allograft tolerance.