Liver Immunology

Project Leader: Dr Patrick Bertolino

The Liver Immunology Group is hoping to determine whether it is possible to influence the balance between tolerance and immunity in liver transplantation by influencing naïve T cell trafficking. Understanding these mechanisms would provide new strategies to enhance the survival of liver transplants and other solid organ transplants without immuno-suppression.

Research focus

The research of our group is focused on the liver, an organ with unique tolerogenic properties. In many species, liver transplants are spontaneously accepted across a complete MHC mismatch and some viral infections, such as the one by the Hepatitis C virus, become chronic suggesting that the virus exploit this liver property to persist in the host.

The mechanisms involved in these processes remain unknown. The broad aims of our group are to understand the interactions between T lymphocytes and hepatic cells, the parameters that determine the balance between tolerance and immunity in the liver as well as those leading to chronic hepatitis.

We are particularly interested in dissecting complex mechanisms of liver-induced tolerance of CD8+ T cells, which are responsible for graft rejection and virus clearance.

Our results have demonstrated that due to its unique architecture and slow blood flow the liver can retain and activate naïve CD8+ T cells, therefore acting as a site of primary activation. This finding contradicts the general accepted view that primary T cell responses can only be initiated in lymphoid tissues (lymph nodes and spleen). It is the first demonstration that a non-lymphoid organ can be the site of primary activation, a seminal finding with important implications for liver transplantation and Hepatitis C virus (HCV) research.