Immune mechanisms contributing to spontaneous acceptance of liver transplants in rodents and their potential for clinical transplantation
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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.
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M. den Dulk, AW Morrow Gastroenterology and Liver Laboratory, Centenary Institute, Royal Prince Alfred Hospital and Sydney University, Sydney, Australia