Human Tregs with 'direct' allospecificity can prevent rejection of human hepatocytes in a humanised mouse model.

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Liver transplantation is a successful treatment for patients with severe liver disease. Despite this, the majority of patients are maintained on immunosuppressants (IS) life long with associated side effects, affecting long term outcome. The goal of this study is, therefore, to devise protocols to enable the patient to accept their graft without the need for long term use of IS. Interestingly, populations of immune cells in the recipient, called regulatory T cells, have been shown to regulate the patient‘s immune system and prevent against organ rejection. The aim of our research is to develop new treatments that involve increasing the number of these cells in the recipient. We will a. isolate these cells from the recipient, expand them and ensure they are stable in culture. b. we will ensure they have a ‘specific‘ inhibitory role on the immune system i.e. they prevent liver rejection, but do not cause general/total immunosuppression c. We will use animal models of liver transplantation to show the safety and efficacy of these cells before re-introduction into the patient. This work will pave the way towards the development of protocols to induce tolerance, leading to more individualized treatment and minimize the complications of long term immunosuppression.