B5 - Antigen specificity and function of tissue infiltrating T cells in autoimmune liver disease
Dr. med. Christina Weiler-Normann
I. Department of Internal Medicine
University Medical Center Hamburg-Eppendorf
Autoimmune hepatitis (AIH) is an immune-mediated, inflammatory liver disease that leads to fibrosis and cirrhosis as well as its complications if left untreated.
Up to now the etiology and pathogenesis of AIH have been insufficiently understood. But it seems that in particular T cells are responsible for the hepatocellular damage. Nonetheless, the autoantigens, which those T cells recognize, have not been identified in the vast majority of AIH patients. The determination of those T cell antigen specificities could help to develop a specific AIH therapy. This is of peculiar interest since the current standard therapy of AIH is based on the undirected administration of immunosuppressive agents that suppress all activities of the immune system.
B5 in 60 SecondsVideoarchivonline seit 25.11.2012
In our previous studies we have shown that inflammatory CD4+ T cells are main drivers in the pathogenesis of AIH. We could demonstrate that T cells isolated out of the peripheral blood as well as out of the liver of AIH patients show an increase of inflammatory mediators.
In order to identify the target antigens of liver-infiltrating CD4+ T cells – that means the molecular target structures of the pathogenic immune response – of AIH patients, antigen specificities of these cells need to be investigated by employing combinatorial peptide libraries in the positional scanning format. This provides on the one hand the possibility of better understanding the etiology and pathogenesis of AIH and on the other hand the opportunity to find potential new therapeutic approaches.