Cracking organ rejection
Organ transplants could save the lives of many patients, but the ultimate rejection of the organ remains a stubborn problem. The immune system is the main culprit because it is designed to destroy invading microorganisms or other foreign matter. Immune cells recognize transplanted organs as foreign because of minor genetic differences between the donor and recipient that result in a destructive attack on the organ. Chemical immunosuppressants such as cyclosporin A, which dampen-down the immune system, can prevent short-term or “acute rejection” in the first year after transplantation. However, long-term or “chronic rejection” beyond the one-year mark remains high, despite continuous administration of these drugs. The mechanisms behind chronic rejection are still obscure, making the development of new therapies to specifically induce long-term acceptance difficult. In the July issue of Nature Immunology (Vol. 2, No. 7, pages 591-596), scientists at Millenium Pharmaceuticals in Boston explored the role of a “costimulatory” protein on T cells called ICOS. They found ICOS plays a key role in both acute and chronic rejection. Using a mouse transplant model, they show that two weeks of ICOS blockade and cyclosporin A treatment not only prevents acute rejection but also leads to long-term acceptance of the transplant. This basic investigation into the mechanism of rejection has thus provided a promising new approach that can be considered for the prolongation of transplants. A News & Views on this article was written by Jeffrey A. Bluestone of the University of California, San Francisco, Head of the National Immune Tolerance Network (pages 573-574). Wayne W. Hancock Millenium Pharmaceuticals, Inc. Biotherapeutics 75 Sidney Street Cambridge, MA 02139 UNITED STATES Tel: (+1) 617-551-3637 Fax: (+1) 617-679-7071 whancock@mpi.com Jeffrey A. Bluestone University of California - San Francisco UCSF Diabetes Center 513 Parnassus Ave. Room HSW 1114, Box 0540 San Francisco, CA 94143-0540 UNITED STATES Tel: (+1) 415-514-1683 Fax: (+1) 415-476-1660 jbluest@diabetes.ucsf.edu (C) Nature Immunology press release.
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