Intestinal failure, where the gut fails to absorb sufficient nutrients, is a debilitating condition which requires treatment with intravenous parenteral nutrition. Unfortunately, this treatment can be complicated by severe infections and venous blood clots, and in such circumstances intestinal transplantation can be an effective treatment. However intestinal transplantation suffers from high rates of graft rejection, as well as cases of graft versus host disease (GVHD) and has only a 60% 5-year survival.
Large numbers of immune cells from the donor are transferred into an intestinal transplant, and the interactions of the immune cells from donor and recipient, the survival of donor immune cells in the transplant, and the mechanisms that allow colonisation of the transplanted tissue by recipient immune cells are not well understood. Our work will study these questions through studying intestinal immune cell populations in recipients of intestinal transplants at the Oxford University Hospitals NHS Foundation Trust transplantation unit, one of only two centres offering adult intestinal transplantation in the United Kingdom. These results will have direct patient benefit by elucidating the mechanisms that drive graft rejection and GVHD in intestinal transplantation, and by identifying strategies that might prevent these complications. Moreover, these results may provide insights into more fundamental questions in human immunology, including the dynamics of tissue residency of immune cells in the gut.