Transforming growth factor beta1-modified donor cell transfusion induced allo-heart tolerance

The therapeutic value of the transforming growth factor beta 1 (TGF-beta1) in transplantation has been reported; however, cell-mediated gene therapy using TGF-beta1 is not a widespread application in organ transplantation. This study was performed to evaluate whether TGF-beta1-modified donor spleen cell-specific transfusion could induce tolerogenicity and prolong allograft survival in rat heterotopic heart transplantation. Stable TGF-beta1-transduced spleen cells were established. Wistar rat splenic T-cell responses to donor spleen cells that received TGF-beta1-transduced were severely impaired. Survival of Sprague-Dawley cardiac allografts in Wistar rats given TGF-beta1-modified donor spleen cells (5 x 10(6), 7 days before transplantation), was extended modestly but significantly. Liposome transduction of donor spleen cells to overexpress TGF-beta1 is associated with marked impairment of their T-cell allostimulatory activity but only modest prolongation of allo-heart survival.