Organ transplant rejection is a fear for many people faced with a possible need for transplantation. For this group of transplant candidates, some good news has come from recent research taking place at the Emory Transplant Center. Emory’s research shows that a new immunosuppressant protocol could convince a transplant recipient’s immune cells to switch sides by converting cells that normally recognize and attack transplanted organs to cells that control the immune response instead—and protect the grafted organ. This may give patients a better chance of avoiding rejection of the transplanted organ and help them wean off anti-rejection drugs over time, reducing the rate of long-term complications after transplant.
Emory’s Dr. Mandy Ford, assistant professor of surgery, is the senior author on the study, published this month in the Proceedings of the National Academy of Sciences Early Edition. The National Institute of Allergy and Infectious Diseases funded the study.
Emory transplant researchers found that an experimental combination of treatments can induce turncoat behavior among immune cells in mice with skin grafts. The combination included a transfusion of spleen cells from the donor, as well as a limited course of a drug that blocked immune cell signals from the CD154 molecule. The grafts survived for months. If one part of the combination was deleted, then the grafts didn’t last more than a few weeks.
“Using this treatment protocol, we found that a subset of cells that would normally attack the graft instead turn on a gene that instructs them to become graft-protective,” Dr. Ford says. “These protective cells, called regulatory T cells, are present in everyone’s immune system and normally prevent us from developing autoimmunity.”
Unfortunately, using drugs that block CD154 clinically in humans has the drawback of causing blood clots. But Dr. Ford says that Emory researchers are investigating the possibility of blocking CD154 signals in a different way to avoid the blood clotting mechanism, such as using donor-specific transfusions to control the immune system. The Emory Transplant Center is currently studying donor-specific transfusion (but with different drugs, not anti-CD154 drugs) as part of an experimental kidney transplant protocol.
We’ll keep you updated on this innovative transplant research. If you have questions on this research for our team, or thoughts you’d like to contribute, please feel free to use the comments section below!
- Emory Transplant Center website
- Abstract of study: Antigen-specific induced Foxp3+ regulatory T cells are generated following CD40/CD154 blockade