Immune mechanisms contributing to spontaneous acceptance of liver transplants in rodents and their potential for clinical transplantation.

The fate of organ transplants between unrelated individuals of the same species is almost always rejection 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 naïve T cells and liver parenchymal cells; the atypical leukocyte populations of the liver-particularly immature dendritic cells; neutralization of rejection by donor soluble MHC antigen; establishment of microchimerism by donor hematopoietic stem cells; and death by "neglect" of recipient T cells in response to inappropriate activation by donor liver leukocytes. 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 leukocytes 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 leukocyte-induced deletion of liver-reactive T cells. These findings suggest novel ways to explore improved treatment for transplant patients, including the administration of donor leukocytes at the time of transplantation and the delay of some components of immunosuppressive-drug induction therapy.