Role of hepatocytes in inducing primary CD8+ T cell activation and tolerance

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/115030

Funding Status
Closed

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Funded Activity Summary

It is well known that tolerance to liver allografts is more readily achieved than to other organ grafts, even across a major histocompatibility (MHC) barrier. According to some experiments, preferential tolerance to liver grafts may be due to development of chimerism involving the very large number of passenger leukocytes of donor hematopoietic origin present in an organ of this size. However, such a concept does not explain all the available data, particularly those relevant to CD8+ T cells, the primary effectors of graft rejection. Moreover, it does not take into account the fact that the liver possesses a unique fenestrated endothelium which is permeable to naive as well as activated T cells, nor the tolerogenic properties of hepatocytes themselves. Our recent experiments suggest that the liver is a site of primary activation for CD8 T cells and that a normal liver contains a significant number of self-reactive CD8+ T cells. The aim of this project is to determine whether activation of CD8+ T cells by hepatocytes contributes to the striking ability of liver grafts to be accepted and to induce tolerance in the CD8 T cell compartment. This would indicate that the liver plays an important role in peripheral tolerance of CD8+ T cells, providing the basis for novel therapies in transplantation and the treatment of autoimmune diseases. Moreover, this project also aims to generate a unique animal model of chronic liver inflammation in the absence of viral infection. Such a model is needed to study cirrhosis and hepatocarcinoma in the absence of potential oncogenes carried by viruses such as hepatitis B.

Funded Activity Details

Start Date: 01-01-2000

End Date: 01-01-2002

Funding Scheme: NHMRC Project Grants

Funding Amount: $159,662.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Clinical sciences not elsewhere classified

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

CD8 T lymphocytes | Hepatocarcinomas | Liver and hepatocytes | autoimmune and viral Hepatitis | autoimmunity | liver autoimmune diseases | tolerance | transgenic mice | transplantation

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