Targeting the complement system in transplantation

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Complement consists of a normal set of circulating proteins whose role in fighting infection is long established, but which is also now known to impede the acceptance of healthy foreign tissue such as a kidney transplant. Complement seems to work together with more sophisticated elements of the immune response called T lymphocytes, and we now believe that collaboration between complement and T cells is essential for graft rejection. It follows that blocking the alliance between complement and lymphocytes may hold a key to a new method of treatment, which could lead to more effective prevention of graft rejection and allow lower use of toxic drugs that are directed against T lymphocytes. However in order to plan effectively, we need better understanding of the cells that produce and secrete complement and how complement enhances the performance of these cells to stimulate T lymphocytes. From a shortlist of two cell types transferred with the donor kidney, we propose to examine the relative importance of these cells types in triggering graft rejection. We also have strategies for reducing the secretion of complement by these cell types, and wish to see if we can build this into a treatment strategy suitable for clinical therapy. More effective ways to prevent rejection crises would be expected to cut graft losses in the short and long term, and thus lead to a significant health and economic benefit associated with transplant success.