The holy grail of transplantation biology is how to prevent organ-specific graft rejection in transplant recipients without compromising their ability to fight infections. Currently, transplant patients face a life-long battle to control their immune system; this requires that they use strong immunosuppressive drugs that may leave them unable to fight off infection by viruses or bacteria.
In the March issue of Nature Immunology, researchers unravel how a type of suppressor immune cell induces donor-specific immune cell nonresponsiveness -- known as tolerance -- in transplant recipients and can thus prevent graft rejection.
Nicole Suciu-Foca and colleagues at Columbia University identified a suppressor T cell population that can be generated from peripheral blood cells upon repeated exposure to donor tissue. These suppressor T cells induced the expression of inhibitory receptors -- called immunoglobulin-like transcript 3 (ILT3) and ILT4--on antigen-presenting cells (APCs); these ILTs rendered the APCs unable to activate potentially harmful immune cells against the transplanted organ. Introducing ILT3 or ILT4 into cultured APCs also rendered these cells 'tolerogenic' to the recipients' immune cells, but, importantly, these authors show that this suppression is donor-specific. In patients who had undergone heart transplants, ILT expression in circulating blood cells was also correlated with a lack of rejection episodes. Thus, conditioning of transplant recipients to generate donor-specific suppressor T cells or to induce expression of inhibitory ILT on APCs may achieve lasting organ-specific tolerance.
Dept of Pathology,
Columbia University College of Physicians & Surgeons,
New York, NY,
Tel: +1 212 305 6941
Additional contact for comment on paper:
Mark B. Feinberg
Emory University School of Medicine,
Atlanta, GA, USA
Tel: +1 404 727 4374
(C) Nature Immunology press release.
Message posted by: Trevor M. D'Souza