Role of IFN-gamma in allograft rejection

Abstract

Interferon (IFN)-gamma is a cytokine produced mostly by activated T cells and NK cells that has complex effects on immune and nonimmune cells. IFN-gamma plays important roles in inflammation, usually in synergy with other cytokines, such as IL-1beta and TNF-alpha. The uniqueness of IFN-gamma lies in its ability to induce major histocompatibility complex (MHC) expression in many tissues, making it particularly relevant to transplantation. The results of graft rejection in the absence of IFN-gamma show that IFN-gamma modulates but is not essential for the allogeneic responses, suppressing generation of CTL. In vivo IFN-gamma has a protective role early in the response to vascularized organ allografts: transplants in mice have a tendency to develop necrosis when IFN-gamma is not available, apparently by failure of the microcirculation. The lack of IFN-gamma greatly reduces the induction of MHC in organ allografts, and it is possible that this is indirectly related to the protective effect of IFN-gamma. Nevertheless IFN-gamma also promotes graft vessel disease later in the course ofthe transplant. Thus IFN-gamma has diverse and potentially contradictory effects on organ allograft survival, acting both on the immune system and on the graft itself, the net effect depending on the graft type and the time post-transplant.