| Regulatory T cells (Treg) are essential in the induction and maintenance of tolerance to grafted organs. Recently, we established in a mouse transplant model, that functional dominance of Treg can be achieved by tipping the balance in favour of regulatory T-cells over alloreactive effector T-cells. It is now our primary aim to exploit this knowledge for clinical purposes and to induce functional Treg dominance by increasing the in vivo Treg pool through adoptive transfer of ex vivo induced and expanded Treg. Therefore, we have developed a novel CFSE based strategy that uniquely allows the induction and purification of highly suppressive human Treg with defined antigen specificity. Importantly, we observed that the purified Treg did not consist of a homogeneous population, but of phenotypic and functionally distinct Treg subsets. So far, we purified two alloantigen-specific subsets, CD27+Treg and CD27-Treg that both reveal potent immunosuppressive capacity, but clearly differ in other aspects. The aim of this proposal is to study these subsets in more detail, to understand the possible implications of this diversity for future clinical therapy. |
