Transplant Protocol Induces Immune Cells to Switch Sides

December 2011

An Emory Transplant Center protocol published in the Proceedings of the National Academy of Sciences Early Edition shows that an experimental combination of treatments can convert immune cells that would normally recognize and attack a transplanted organ into cells that control the immune response. This could enhance the chances of avoiding rejection of the transplanted organ and may help the recipient wean off anti-rejection drugs over time, reducing the rate of long-term complications. Mice with skin grafts were used.

The senior author is Mandy Ford, PhD, assistant professor of surgery at the Emory Transplant Center. First author Ivana Ferrer is a student in Emory's Immunology and Molecular Pathogenesis graduate program.

The treatment combination involved transfusion of spleen cells from the donor and a limited course of a drug that blocked immune cell signals from the CD154 molecule. The animals received no other anti-rejection drugs post-transplant. The skin grafts survived for months, though if one part of the combination were missing, they didn't last more than a few weeks

"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 are called regulatory T cells — they are present in everyone's immune system and normally prevent us from developing autoimmunity. Previously we didn't know whether the treatment was simply enhancing regulatory T cells that were already there, or whether it actually induces the emergence of a new group of graft-specific regulatory T cells."

An opportunity to alter the course of an immune response exists when cells that would normally attack the transplanted organ are activated, which occurs when they come into contact with donor cells. If this happens while CD154 is blocked, the cells either die or convert into regulatory T cells, the Emory team showed.

One obstacle to using drugs that block CD154 clinically is that they can induce blood clots in humans. Dr. Ford says Emory researchers have been investigating alternative methods of blocking CD154 signals.