Targeted Treatment May Prevent Transplant Rejection

Organ rejection is caused by donor dendritic cells being rapidly replaced by the recipient’s cells.

Targeting certain donor cells was associated with a lower risk of organ rejection in mice that had kidney and heart transplants in a recent study.

This new discovery could provide a way to prevent or treat organ transplant rejection in humans. There are currently more than 100,000 people waiting for an organ transplant, and current practices may not ensure a donor organ is accepted by the recipient’s immune system.

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

Successful engraftment currently relies on preventing an immune response from T cells in the lymph nodes and spleen, or in the graft through antirejection drugs, according to a study published by Nature Communications. Transplants are quickly rejected by the body without immunosuppressive treatment, but if T cell activation occurs, stopping rejection becomes difficult, despite preventive treatment.

T cell activation requires help from dendritic cells that present donor-derived antigens to T cells and causes an immune response. Investigators discovered dendritic cells are an important factor that drives rejection of transplanted organs.

In the mice models, dendritic cells from the donor’s heart or kidney grafts were quickly replaced by the recipient’s cells, causing T cell activation in the graft and increasing rejection risk.

“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 co-author of the study Adrian E. Morelli, MD, PhD. “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.”

A next step for investigators would be to develop a novel method to target dendritic cells within transplanted organs that could prevent rejection, the study concluded.