Cellular basis of rejection: Liver is one of the most immune-tolerant of all solid organ transplants. Histological criteria for diagnosis of ACR in liver depends on the presence of large portal based inflammatory infiltrate with injury to hepatic components. Early target tissue for ACR is the bile duct epithelium and venous endothelium leading to injury to hepatocytes either by direct immunological injury or due to the effect of vascular injury and ischemia. Role of CD4+ and CD8+ lymphocytes in ACR: Lymphocytes are the predominant of cells involved in ACR. Hepatic allograft rejection is mediated by a primary response of T-lymphocytes, followed by a mixed inflammatory infiltrate. Lymphocyte population contains both CD4+ and CD8+ lymphocytes, when activated; these cells proliferate, differentiate and secrete cytokines. The appearance of CD4+ lymphocytes within the portal tracts predicts rejection even before the biochemical evidence is present. ACR and chronic rejection correlate with the presence of CD8+ rather than CD4+ cells within the portal tracts. (1) It is believed that CD8+ T cells that cause the graft injury via cytolytic activity directed against donor alloantigen. Clinical observations suggest that CD4+ cells have a central role in allograft rejection by acting through CD8+ effector cells.