New research suggests that organ transplant recipients who reject organs may not necessarily reject future transplanted organs. In a study of mice at the University of Chicago, researchers found the rodents rejected a transplanted heart after a bacterial infection, but then tolerated a second heart transplant after the infection was eliminated from the body.
All organ recipients must take immunosuppressive drugs to keep their bodies' immune systems from rejecting the new organs. However, an infection or illness even years after transplantation and years of immunosuppressive therapy could cause the body's immune system to identify the transplanted organ as a threat, thereby causing rejection.
To this point, doctors have assumed that once the body rejects an organ, there is an increased chance of subsequent rejections since the body's immune system existed in a state of heightened alert. However, the research at the University of Chicago shows this might not necessarily be the case.
"Our results imply that tolerant patients who experience rejection could be treated with short-term immunosuppressive medications to protect the transplant, and then weaned off once tolerance returns. Our results change the paradigm that immune memory of a transplant rejection is invariably permanent," said Anita Chong, Ph.D., professor of transplantation surgery at the University of Chicago in Illinois and co-senior author of the study, which was published in Nature Communications.
In the study, researchers conducted heart transplants on mice and provided the immunosuppressive drugs that kept the mice's bodies from rejecting the organs. Two months later, the mice received injections of listeria bacteria, which caused about half of them to reject the transplanted hearts.
A few days after rejection occurred — and after the listeria had been eliminated from their bodies — the mice successfully tolerated a second heart transplant, as long as the organ was a molecular match for the initial transplanted organ. What's more, the mice didn't need additional immunosuppressive drugs to tolerate the new organ.
The study authors wrote that when the mice first rejected the hearts, there was a high level of certain T cells in their bodies that could have caused the organ rejection. But a few days later, the number of T cells decreased, which could explain why the mice tolerated a second heart transplant.
The study authors wrote that the "experimental evidence of a transplant outcome that does not follow the rules of allosensitization" and shows that a "memory of regulation can dominate over a memory of infection-triggered rejection."
While there's no way to successfully replicate the same experiment in humans, the research team is looking for ways to induce the same result in human transplant patients.
"We're now working to understand in greater detail the mechanisms for how this return of tolerance happens," said author Michelle Miller, a graduate student in molecular medicine at the University of Chicago. "We want to find if there are other mechanisms ... that mediate tolerance and help prevent memory of the rejection."
