Pitt medical researchers help shed light on organ rejection

Organ transplants, while majestic when successful, come with many health hazards — the most glaring being sudden or eventual organ rejection.

An international team of researchers, led by experts from the University of Pittsburgh School of Medicine, published a study Wednesday in the journal Nature Communications that could offer insight into treating or preventing rejection.

The study focused on targeting specific donor cells to determine whether they would lower the risk of organ rejection in mice after undergoing kidney and heart transplants.

“The success of organ transplantation has reached a plateau over the past 10 or 20 years, with a significant proportion of patients still losing their grafts to rejection despite immunosuppressive treatment,” said Dr. Fadi Lakkis, professor of surgery, immunology and surgery at the University of Pittsburgh and co-author of the study. “New methods to tackle rejection are needed, and this discovery is another step toward finding a solution.”

As is the standard with most transplant cases, patients receive anti-rejection drugs after procedures. The drugs prevent the immune system from attacking the new organ's cells and rejecting the organ. Specifically, the drugs halt the activation of T-cells in the lymph nodes and spleen or the transplanted organ.

When T-cell activation takes place, it's much more difficult for doctors to stop rejection.

The study found that heart and kidney donors' white blood cells, known as dendritic cells, in mice are quickly replaced by recipients' dendritic cells after transplants. The process causes proliferation of T-cell activation.

“Our study indicates that eliminating transplant-infiltrating dendritic cells reduces proliferation and survival of T-cells within the graft with the consequent prolongation of transplant survival,” said another co-author, Dr. Adrian Morelli, associate professor of surgery and immunology at the Thomas E. Starzl Transplantation Institute in Pittsburgh.

Morelli told the Tribune-Review that whether this can help prevent organ rejection and failure in human transplant patients remains to be seen.

“I don't want to create false hope or make false promises,” he said. “But these findings open the opportunities for new drug development to interfere with the cells. We still need to learn how to do it.”

Ben Schmitt is a Tribune-Review staff writer. Reach him at 412-320-7991 or bschmitt@tribweb.com.