Project title: Mechanisms of immune regulation by regulatory T cells in liver transplantation.
Regulatory T (Treg) cells are subset of suppressive CD4+ T helper cells important for the maintenance of self-tolerance, suppression of allergic responses, and prevention of rejection reactions after organ transplantation. They are also involved in the suppressive microenvironment of tumours, and promote growth and metastasis. The Tasken/Aandahl group has extensively studied Treg molecular mechanisms of intercellular communication and immune-regulation. There are performed approximately 100 liver transplantations annually at Rikshospitalet and sampling will be done prior to transplantation and 3, 6 and 12 months post transplantation. I will study patients transplanted for primary sclerosing cholangitis (PSC), and patients transplanted due to un-resectable hepatocellular carcinoma (HCC). I want to understand the precise immunosuppressive mechanism of Tregs and explore their functional activity in transplant recipients with respect to disease severity, effects of immunosuppressive medication and the significance of Tregs in rejection reactions 2/10 and graft function. In a second sub-project I will do a comparative studies of liver transplant recipients (PSC vs. HCC), which gives us the opportunity to do comparative studies of Treg function in an autoimmune disease versus a malignancy.
I will investigate the dual role of Tregs in controlling autoimmunity (PSC) versus a malignancy (HCC) and their role in the complex immunological interactions that take place after liver transplantation.
The specific objectives of this project are to:
1. Map signalling pathways inside effector T cells that convey the inhibitory signal from the Tregs.
2. Characterise the immune status in PSC and HCC patients prior to and after liver transplantation.
3. Correlations of immune status prior to transplantation and early post transplantation rejection reactions.
4. Study the effects of immune suppression on Treg function and the T cell repertoire.person:publications: null