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Ann Thorac Surg 1994;57:72-75
© 1994 The Society of Thoracic Surgeons

Articles

Development of tolerance to experimental cardiac allografts in utero

Gary M. Kline, MD, Zhenya Shen, MD, Muhammad Mohiuddin, MD, Vincent Ruggiero, BS, Susan Rostami, BS, Verdi J. DiSesa, MD*

Department of Cardiothoracic Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA

* Address reprint requests to Dr DiSesa, Cardiothoracic Surgery, Medical College of Pennsylvania, 3300 Henry AVC, Philadelphia, PA 19129.

"Actively acquired tolerance" to foreign cells was described in 1953 by Medawar and colleagues and formed the basis for subsequent efforts in organ transplantation. We have applied these historic principles of intrauterine immune manipulation in a vascularized cardiac allograft model. Allogeneic Lewis-Brown Norway (LBN) splenocytes (0 to 5 x 107 cells) were injected intraperitoneally into each fetus of a pregnant Lewis rat at day 14 to 16 of gestation, when T cells are "educated" to distinguish self from foreign. This manipulation causes fetal attrition inversely proportional to the number of cells injected. Heterotopic transplantation using an LBN heart was carried out in each surviving fetus at 6 to 8 weeks of age. Untreated Lewis rats rejected LBN hearts within 7.6 days. Rats receiving LBN splenocytes in utero demonstrated prolongation of graft survival proportional to the number of cells given. Surviving animals exposed to 5 x 107 allogeneic cells in utero (n = 4) had graft survivals of 24 to more than 150 days (mean, 88.C days), significantly longer than control animals (6 to 10 days; mean, 7.6 days; p < 0.02). Significant prolongation of cardiac allograft survival and in some cases complete tolerance can be achieved by intrauterine exposure to allogeneic cells at a critical period of immunologic development. Because many serious cardiac defects amenable to treatment by cardiac transplantation can be detected by ultrasound early in gestation, treatment based on this strategy may become useful in pediatric heart transplantation.




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