A recent study in the journal Nature Communications suggests blocking organ donors' dendritic cells may help prevent organ rejection.

The project, led by doctors at the University of Pittsburgh, looked at whether targeting dendritic cells in mice who received either a heart or kidney transplant would decrease the rate of organ rejection. Tests of this nature have not been conducted on human organ recipients.

"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, co-author of the study. "New methods to tackle rejection are needed, and this discovery is another step toward finding a solution."

"The next step would be to devise methods to specifically target dendritic cells within transplanted organs," Dr. Lakkis continued. "Such methods carry the promise of preventing or interrupting rejection without compromising the patient's overall immune defenses."

Standard protocol calls for organ recipients to receive anti-rejection drugs after transplant procedures. Even with immunosuppressive drugs, the rate of organ transplant rejection remains high. Understanding the mechanisms behind the immune system's response following transplant is key to helping researchers decrease the rate of organ rejection.

When they work, immunosupressive drugs prevent the body's immune system from attacking the transplanted organ's cells, which ultimately leads to rejection. The drugs stop the activation of T cells in the lymph glands, spleen and transplanted organ.

It's important to stop T cells from activating after transplant surgery. Once started, it's difficult to stop the body from rejecting the organ.

To fully activate, T cells must physically contact a highly specialized type of cell called dendritic cells. Following an organ transplant, dendritic cells trigger an immune response in the body by presenting the donor's antigens to the recipient's T cells found in lymphoid tissues.

Researchers found dendritic cells can trigger rejection of transplanted organs by activated T cells that have already entered the transplanted organ. Heart and kidney grafts included the donor's dendritic cells, but they were quickly replaced by the recipient's dendritic cells. This prompted T lymphocyte activation within the graft, thus increasing the risk of rejection.

"We demonstrated that dendritic cells not only exert a key role as antigen-presenting cells in graft-draining lymphoid organs, but also play a critical function within the transplanted organs," said Adrian E. Morelli, M.D., Ph.D., associate professor of surgery and immunology at the Thomas E. Starzl Transplantation Institute and study co-author. "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."

It remains to be seen whether this finding will have an impact in human organ transplants.

"I don't want to create false hope or make false promises," Morelli 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."