Successful kidney transplants rely on the biological compatibility of the donor and recipient but still require long-term use of drugs to tamp down the recipient’s immune system and prevent donor organ rejection. Finding a method to increase compatibility can help recipients tolerate a life-saving organ transplant without the lifelong need for anti-rejection medications.

A relatively recent approach that improves donor and recipient biocompatibility induces tolerance by combining irradiation of part of the kidney recipient’s immune system and an infusion of donor immune cells. This creates a dual immune system in the recipient. However, this approach has only been successful when important features of the donor’s and recipient’s immune systems are identical matches.

Transplant specialists at the University of Wisconsin–Madison and Stanford University have developed the new approach, described in a non-human primate model, that may help kidney transplant prospects even when they are less closely matched to donors and in the absence of immunosuppressant drugs.

The research team, led by Dixon Kaufman, a UW–Madison professor of surgery and director of the UW Health Transplant Center, sought to maintain kidney function without rejection in a monkey model resembling human transplants. They also sought to avoid graft-versus-host-disease, a transplant complication in which immune cells from the donor attack its new host.The experimental transplant protocol, published recently in the journal Transplant International, included 11 monkeys at the Wisconsin National Primate Research Center that were more loosely matched by tissue type than what has previously been accomplished for human donor-recipient pairs.

Two key strings of tissue typing proteins on the surface of cells, known as major histocompatibility antigens, help the immune system recognize parts of its own body as “self.” This protects the body from invaders that have different tissue antigens and are recognized as “non-self,” thus setting off an immune response. The monkeys in the tolerance induction study had just one match among the two key protein strings, while human transplant pairings previously successful with tolerance induction required two matches.