Basic mechanism of spontaneous tolerance of liver allografts in a rat model. [ 2004 - 2006 ]

Research Grant

Researchers: Dr Alex Bishop (Principal investigator) ,  A/Pr Alexandra Sharland ,  Dr Chuanmin Wang ,  Prof Geoffrey Mccaughan ,  Prof John Rasko

Brief description Many thousands of Australians have a failing liver and the only treatment for this is a liver transplant. Liver transplantation is a major life-saving strategy and hundreds of Australians are rescued each year who would otherwise have died. Rejection of the transplant is the major problem affecting these patients. This project investigates an animal model where a transplanted rat liver is not rejected, even though the recipient receives no treatment. Previous studies from our group have shown that acceptance is due to donor white blood cells transferred with the liver and based on this finding we are developing treatments that can be used in transplant patients. The current application for funding tests another breakthrough that we have recently made, that treatment of the recipient with a substance called interleukin 4 prevents liver acceptance. This finding shows that interleukin 4, which was previously thought to be involved in preventing transplant rejection, is actually involved in stimulating rejection of the liver. It might therefore be possible to prevent rejection by altering the pattern of its expression, for example, by using an antibody to remove it. This application also aims to examine the overall expression of a very large number of genes in liver transplant acceptance compared with rejection. This will use a new technology called gene array analysis to examine expression of at least 5,000 genes to identify those that are increased during liver acceptance. In addition, gene therapy will be used to increase expression of a single gene called IDO that we and others have found to be associated with transplant acceptance. This gene will be expressed in white blood cells of the liver donor after transplantation to promote liver acceptance and prevent rejection. Ultimately it is intended that these findings will be used to prolong the survival of liver transplant patients by revealing new ways to prevent rejection of liver transplants.

Funding Amount $AUD 374,625.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant