New immunologic insights into mechanisms of allograft rejection

Abstract

Our current understanding of liver allograft rejection indicates that multiple cellular interactions, involving a variety of cell-associated and soluble mediators, are critical to the response. The extravasation and localization of recipient immune cells to the allograft is dependent on recognition and interaction of complementary adhesion molecules expressed on circulating leukocytes and endothelium. Similar receptor-ligand pairs can also augment the binding of effector cells to target tissue within the allograft. Inflammatory mediators such as IL-1, IL-6, TNF-alpha, and IFN-gamma produced within the allograft can increase the local expression of adhesion molecules and thereby promote the entry of specific and nonspecific cells. The TCR expressed on T lymphocytes has the potential to recognize MHC antigens expressed on the allograft in many different forms. Thus, the T cell response to graft-associated alloantigens appears to be complex and dynamic. The production of T cell-derived cytokines is central to the activation and maturation of effector cells within the allograft. The identification of cytotoxic mediators such as serine protease and MBP within rejecting human allografts supports the role of cytotoxic T cells and eosinophils as effector cells. Undoubtedly, the development of genetically manipulated animal models will serve to further elucidate our understanding of the cellular mechanisms of graft rejection.