- Dr. Robert L. Fairchild, Principal Investigator
- Cleveland Clinic Foundation, Cleveland, USA
- Short-Term Therapies Directed at Inflammation and T Cell Activation
Rejection of organs transplanted to treat end-stage heart and kidney disease remains a serious problem in medicine leading to loss of the transplanted organ and the potential death of the patient if a new organ is not available. To inhibit rejection, patients are faced with taking immunosuppressive drugs every day that create many new problems including increased susceptibility to infection and malignancy. These problems have necessitated the design of other strategies to inhibit transplant rejection. The facet of allograft rejection not attenuated by current immunosuppression strategies is the overt inflammation imposed on the graft at the time of the transplant operation. Surgical tissue trauma and other events inherent in the operation quickly induce recipient leukocytes to infiltrate the allograft tissue. Studies from this laboratory have used a heart transplant model in mice to show that this early infiltration causes considerable tissue damage and facilitates the recruitment of cells that eventually mediate rejection of the heart graft.
We have recently observed that attenuation of this early leukocyte infiltration with a 3-day course of therapy directed at the cells that mediate rejection inhibits the rejection of the allografts. The experiments in this proposed study are designed to understand the underlying mechanisms that prevent rejection of the heart grafts in this model. Complete understanding of the components and mechanisms underlying the abrogation of cardiac allograft rejection using this strategy will allow us to extend these studies into other models where the clinical potential of this novel strategy can be tested and may lead to the ability to avoid the immunosuppressive drugs currently used to inhibit rejection.