Liver alloimmunity

The development of immunologic laboratory techniques in such areas as immunohistochemistry, fluorescence-activated cell sorting (FACS), tissue culture and cloning, monoclonal antibody (mAb) production, and molecular biology have allowed more in-depth investigation of the major histocompatibility complex (MHC) and the immunology of allograft rejection. One of the most striking findings from intensive research of cardiac, kidney, liver, skin, and lung transplantation is the existence of significant diversity in the host’s immune response to different organ allografts from the same donor. Such organ-specific differences in graft immunogenicity and/or host and graft interaction are most pronounced in clinical and experimental liver transplantation. Similarly, alloimmune pathways operational for vascularized organ allografts may be quite distinct from parenchymal cellular transplants. Thus, it appears that studies which are directed to prolong the survival of a specific graft must study the specific organ or cell population of interest rather than infer similar mechanisms based on the results of studies from a different endorgan or cell population. In order to study liver alloimmunity, we will review the expression of MHC antigens of various cell populations in the liver of humans in the normal state and after transplantation during periods of quiescence as well as in the setting of acute liver allograft rejection. Furthermore, the histology of liver allograft rejection provides insight into potential alloimmune mechanisms involved in the rejection process. The results of clinical studies have the advantage of being directly applicable to transplantation of various allografts in humans, but at the same time carry the disadvantage of producing variable results due to variation in the human study population. Experimental systems employing various animal models to study liver alloimmunity can be more precisely controlled than clinical studies to answer specific questions, but the results may not be directly applicable to humans; nevertheless, results from experimental systems guide the design of clinical studies.