Writing in the Journal of Clinical Investigation today, researchers from the University of Cambridge, the University of Edinburgh, Lorantis Ltd and Imperial demonstrate that it is possible in mice to alter whether T white blood cells specialise to attack foreign tissue and thus cause rejection, or instead become part of the body's peacekeeping force, which patrols the body, defending against attack.
Unlike current therapies, which leave patients vulnerable to infection by inducing non-specific immunosuppression, this new approach targets a key cellular signal known as Notch, which the researchers found acts as a gatekeeper by governing how immune cells specialise.
Results show that exposing the mice to a combination of the Notch signal and material from the donor two weeks in advance of transplantation stimulates an immune response and significantly increases transplant acceptance from 20 to up to 80 days.
Professor Maggie Dallman of Imperial's Centre for Molecular Microbiology and Infection, and senior author of the paper, said:
"Today, even with extensive efforts to find the best possible immunological match between donor and recipient, organ transplantation resigns the recipient to a lifetime of powerful immunosuppressive drugs that have many unwanted side effects.
"Increasingly organ transplants in the case of kidneys, liver or lung tissue occur between living relatives so you know in advance who the donor and recipient are. Our strategy opens up the possibility of offering gentler postoperative therapy by redirecting the recipient's immune system in advance of the transplant."
T cells are the arm of the immune system that patrol the body, seeking out and destroying diseased cells. There are two key typ
Contact: Judith H Moore
Imperial College London