Apoptosis as a mechanism of tissue injury in liver allograft rejection

Recent studies suggest that apoptosis is an important mechanism of cell dea th in the rejection of liver allografts and that infiltrating host lymphocy tes mediate this process. The first section of this chapter addresses the c ells and molecules that initiate the immune response following transplantat ion of a liver allograft. The recognition of donor alloantigens by infiltra ting host lymphocytes stimulates a cascade of immune events which culminate in development of the effector,cells that mediate tissue damage. Studies w hich demonstrate that apoptosis of hepatocytes and bile duct cells accompan y allograft rejection are detailed in the second section of this chapter: T he final section discusses the potential pathways which lead to apoptosis i n liver allograft rejection. The contributions of the granule-exocytosis pa thway, the Fas-mediated pathway, and cytokines to the induction of apoptosi s in liver allografts are discussed. In addition, the concept that alloreac tive graft infiltrating cells are deleted by apoptosis is presented. A furt her understanding of the mechanisms involved in apoptosis will lead to uniq ue approaches toward the goal of achieving allograft tolerance.