Treating a transplant patient in advance of the operation with cells from the donor could reduce the need for powerful drugs afterwards.
Live donor transplants are becoming more common
The treatment "redirects" the immune system so it does not launch an attack on the donor organ.
Researchers from three UK universities have found a key gene signal that may help protect the new kidney.
The study, published in the Journal of Clinical Investigation, could lead to fewer side-effects for patients.
The number of organs transplanted from live donors is increasing as other supplies of organs diminish.
However, in the absence of a perfect match, patients still have to take high doses of drugs to suppress their immune systems so the organ is not rejected.
Taking such high doses of drugs is counterproductive - they may even increase the chances of cancer in some cases - and scientists are looking for alternative ways to reduce the chance of immune rejection.
The team from Cambridge and Edinburgh universities, and Imperial College London, may have found a way to change the manner in which the body responds to a new organ.
They have found a key chemical signalling system, called Notch, which appears to govern how immune cells develop.
When they exposed mice to a combination of this signal, and material from the donor-to-be, about two weeks before the actual transplant operation, they generated an immune response.
However, when it came to putting in the new organ, they found that the immune system, rather than attacking it, seemed to have been "educated" to turn a blind eye.
Mice given a heart transplant following such treatment found that the length of time the new organ stayed unmolested by the immune system increased fourfold compared with untreated animals.
The treatment appears to encourage the development of one type of immune cells - T suppressor cells, that put the brakes on any immune response.
It also seems to reduce production of T helper cells, which help drive powerful immune reactions.
Professor Maggie Dallman, from Imperial College, was one of the scientists leading the experiments.
She said: "Today, even with extensive efforts to find the best possible immunological match between donor and recipient, organ transplantation consigns 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."
Dr Anthony Warrens, a specialist in renal medicine and immunology at London's Hammersmith Hospital, said that it might be possible to use a variety of methods to reduce the need for immunosuppression drugs in the future.
"We already offer a very good service to transplant patients - we're just looking to make it better."
He said that the problems caused by long-term immunosuppression - cancer, vulnerability to infection and accelerated heart disease, meant that one of the main reasons for transplant "failure" was the death of the patient from other causes, even though the transplanted organ remained in good condition.
Another method being investigated, he said, was giving a "mini" bone marrow transplant prior to the operation to reprogramme the immune system - or even a short course of treatment to the would-be donor which reduces the risk of rejection.
"This represents a huge opportunity to benefit patients."