Transforming Growth Factor β1–Modified Donor Cell Transfusion Induced Allo-Heart Tolerance

Abstract The therapeutic value of the transforming growth factor beta 1 (TGF-β1) in transplantation has been reported; however, cell-mediated gene therapy using TGF-β1 is not a widespread application in organ transplantation. This study was performed to evaluate whether TGF-β1-modified donor spleen cell-specific transfusion could induce tolerogenicity and prolong allograft survival in rat heterotopic heart transplantation. Stable TGF-β1-transduced spleen cells were established. Wistar rat splenic T-cell responses to donor spleen cells that received TGF-β1-transduced were severely impaired. Survival of Sprague-Dawley cardiac allografts in Wistar rats given TGF-β1-modified donor spleen cells (5 × 10 6 , 7 days before transplantation), was extended modestly but significantly. Liposome transduction of donor spleen cells to overexpress TGF-β1 is associated with marked impairment of their T-cell allostimulatory activity but only modest prolongation of allo-heart survival.