PITTSBURGH, Penn., July 10 -- Genetically altered dendritic cells (DCs) could significantly improve the body's acceptance of a transplanted organ, according to University of Pittsburgh researchers in reports made at the 17th World Congress of the Transplantation Society held July 12-17 in Montreal. Known as the pacemakers of the immune system, DCs are specialized white blood cells that regulate the activity of other immune cells within the body. In the case of organ transplantation, investigators are harnessing DCs to teach T cells to tolerate transplanted organs that would normally be recognized by the body as foreign.
"DCs can be manipulated to disable the host's T cell response to a new organ," noted Angus Thomson, Ph.D., D.Sc., F.R.C.Path., professor of surgery and director of transplant immunology at the University of Pittsburgh's Thomas E. Starzl Transplantation Institute.
One catch, however, is that donor dendritic cells transplanted together with an organ carry the same tissue markers that spur the host's immune system to reject a new graft. In effect, they could suffer rejection similar to a new organ, according to Dr. Thomson. In an animal transplant model, Pitt researchers circumvented this potential snag by genetically modifying donor-derived dendritic cells to churn out their own local supply of immunosuppressants.
"The benefits are two-fold," explained Dr. Thomson. "First, by producing their own localized immunosuppressant, dendritic cells buy enough time to teach host T cells not to attack and 'evict' the new organ, as it were. Second, the immunosuppressants also dampen the attack of T cells on the new organ. And because these dendritic cells produce immunosuppressants at a local, rather than systemic level, this engineered process minimizes side effects such as infection associated with systemic delivery of immunosuppressants."