21. Grossi P, Minoli L, Percivalle E, Irish W, Vigano ` M, Gerna G. Clinical and virological monitoring of human cytomegalovirus infection in 294 heart transplant recipients. Transplantation 1995; 59: 847. 22. Grossi P, Dalla Gasperina D, Comolli G, et al. Prevalence and outcome of hepatitis C virus infection in a series of 509 thoracic organ transplant recipients. J Heart Lung Transplant 1997; 16: 109. 23. Connell WR, Kamm MA, Ritchie JK, Lennard-Jones JE. Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience. Gut 1993; 34: 1081. 24. Cummins D, Sekar M, Halil O, Banner N. Myelosuppression asso- ciated with azathioprine-allopurinol interaction after heart and lung transplantation. Transplantation 1996; 61: 1661. 25. Scott JP, Hingenbottam JW. Adverse reactions and interactions of cyclosporin. Med Toxicol Adverse Drug Exp 1988; 3: 107. 26. Bacialugo A, van Lint MT, Tedone E, et al. Early treatment of CMV infections in allogenic bone marrow transplant recipients with foscarnet or ganciclovir. Bone Marrow Transplant 1994; 13: 753. 27. Momin F, Chandrasekar PH. Antimicrobial prophylaxis in bone marrow transplantation. Ann Intern Med 1995; 123: 205. 28. Zoumbos NC, Djeu JY, Young NS. Interferon is the suppressor of hematopoiesis generated by stimulated lymphocytes in vitro. J Immunol 1984; 133: 769. 29. Arbustini E, Dal Bello B, Morbini P, et al. Factors increasing the risk of allograft vascular disease in heart transplant recipi- ents. G Ital Cardiol 1997; 27: 985. 30. Opelz G, Wujciak T. The influence of HLA compatibility on graft survival after heart transplantation. The Collaborative Trans- plant Study. N Engl J Med 1994; 330: 816. 31. Kirsch M, Baufreton C, Naftel DC, Benvenuti C, Loisance DY. Pretransplantation risk factors for death after heart trans- plantation: the Henri Mondor experience. J Heart Lung Trans- plant 1998; 17: 268. 32. Koelling TM, Semigran MJ, Mijller-Ehmsen J, et al. Left ven- tricular end-diastolic volume index, age, and maximum heart rate at peak exercise predict survival in patients referred for heart transplantation. J Heart Lung Transplant 1998; 17: 278. Received 20 August 1998. Accepted 11 November 1998. 0041-1337/99/6706-846/0 TRANSPLANTATION Vol. 67, 846 – 854, No. 6, March 27, 1999 Copyright © 1999 by Lippincott Williams & Wilkins, Inc. Printed in U.S.A. REVERSAL OF NATURALLY OCCURRING DIABETES IN PRIMATES BY UNMODIFIED ISLET XENOGRAFTS WITHOUT CHRONIC IMMUNOSUPPRESSION 1 FRANCIS T. THOMAS, 2 CAMILLO RICORDI, 3 JUAN L. CONTRERAS, 2 WILLIAM J. HUBBARD, 2 XIAO LING JIANG, 2 DEVIN E. ECKHOFF, 2 SAMUEL CARTNER, 4 GUADALUPE BILBAO, 5 DAVID M. NEVILLE,JR., 6 AND JUDITH M. THOMAS 2,7 Division of Transplantation Immunology, Department of Surgery, Department of Comparative Medicine, and The Gene Therapy Program, University of Alabama at Birmingham, Birmingham, Alabama 35294; The Diabetes Research Institute at the University of Miami, Miami, Florida 33136; and the Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland 20800 Background. Isolated pancreatic islet transplanta- tion (IPITx) is an attractive alternative for treatment of insulin-dependent diabetes mellitus (IDDM). How- ever, IPITx has been difficult to implement clinically because islets frequently fail to function, have a high incidence of rejection, and are susceptible to autoim- mune recurrence and damage by chronic immunosup- pressive therapy. Tolerance induction may be a ratio- nal approach to resolve several of these limitations. Because anti-CD3 immunotoxin (IT) has been success- ful in promoting stable primate kidney transplant tol- erance in our experience, we considered that toler- ance induction with IT might be duplicated in IPITx. Materials and Methods. Three monkeys with spon- taneous IDDM (two Macaca fascicularis and one Ceropithecus aethiops) were treated with xenoge- neic pancreatic islets (Macaca mulatta). Intrahe- patic islet transplantation was performed at a mean of 131363860 islet equivalents/kg. Islet xenograft acceptance was accomplished by tolerance induc- tion with two injections of IT given on day 0 at 2 hr before transplantation and on day 1, respectively. IT treatment was supplemented with cyclosporine 1 This work was supported in part by a Juvenile Diabetes Foun- dation International grant to F.T.T., NIH grants R01 AI 122293 and AI 39793 to J.M.T., and a cooperative research and development agreement from Novartis to J.M.T. 2 Division of Transplantation Immunology, Department of Sur- gery, University of Alabama at Birmingham. 3 The Diabetes Research Institute at the University of Miami. 4 Department of Comparative Medicine, University of Alabama at Birmingham. 5 The Gene Therapy Program, University of Alabama at Birming- ham. 6 The Laboratory of Molecular Biology, National Institute of Men- tal Health. 7 Address correspondence to: Judith M. Thomas, PhD, University of Alabama at Birmingham, BDB 802, 1808 7th Avenue South, Birmingham, AL 35294. E-mail: jthomas@uab.edu TRANSPLANTATION 846 Vol. 67, No. 6