Transplantation therapies have revolutionized care for patients with
end-stage organ (kidney, liver, heart, lung, and pancreatic β-cell) failure,
yet significant problems persist with treatments designed to prevent graft
rejection. Antirejection therapies are not always effective, must be taken
daily, and are both expensive and associated with well-known toxic effects.
Recent advances have suggested that the immune system has more self-regulatory
capability than previously appreciated. In this review, we discuss immune
system function and new therapeutic agents that modify so-called costimulatory
receptor signaling to support transplant function without generally suppressing
the immune system.