The fate of organ transplants between unrelated individuals of the same species is almost always to be rejected, unless the recipient receives immunosuppressive drugs. Liver transplants are an exception, as in a number of animal models, they are often accepted without requiring any treatment. Several mechanisms have been proposed for liver transplant acceptance including: the vascular structure of the liver which allows interaction between na?ve T cells and liver parenchymal cells; the atypical leucocyte populations of the liver particularly immature dendritic cells; neutralisation of rejection by donor soluble MHC antigen; establishment of microchimerism by donor haematopoietic stem cells and death by ?neglect? of recipient T cells in response to inappropriate activation by donor liver leucocytes. Although all these mechanisms may contribute to liver acceptance to some degree, an important finding is that liver acceptance appears to be mainly due to donor leucocytes transplanted with the liver. In combination with the observation of rapid T cell activation followed by their death after liver transplantation, these findings have identified a prominent role for donor leucocyte-induced deletion of liver-reactive T cells. These findings suggest novel ways to explore improved treatment for transplant patients, including administration of donor leucocytes at the time of transplantation and delay of some components of immunosuppressive drug induction therapy.
CD40, a member of the growing tumor necrosis factor receptor (TNF-R) family of molecules, functions as a transmembrane signal receptor in both hematopoietic and non-hematopoietic cell types, although its physiological roles are less well understood in the latter. Much has been learned over the past decade about the role of CD40 signaling in various cellular functions. In addition, some of the molecular events which occur subsequent to CD40 engagement have been characterized, although much remains to be understood. This review will summarize the known important biological roles of CD40, and discuss what is currently known about how CD40 signals.
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.