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Can T-Cell Costimulatory Pathway Modifiers Revolutionize the Prevention of Graft Rejection?

David M. Harlan, MD; Allan D. Kirk, MD, PhD

JAMA. 1999;282:1076-1082.

Transplantation therapies have revolutionized care for patients with end-stage organ (kidney, liver, heart, lung, and pancreatic -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.

Author Affiliations: Navy Medical Research Center, NIDDK/Navy Transplantation and Autoimmunity Branch (Drs Harlan and Kirk), and the Uniformed Service University of the Health Sciences (Dr Harlan), Bethesda, Md; and the Organ Transplant Service, Walter Reed Army Medical Center, Washington, DC (Dr Kirk).

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