Gene Transfer of Transforming Growth Factor-β1 Prolongs Murine Cardiac Allograft Survival by Inhibiting Cell-Mediated Immunity

Abstract

Overview summary Transforming growth factor-β1 (TGF-β1) is an immunosuppressive cytokine that negatively regulates a variety of immune responses. The inhibition of host immune responses by TGF-β1 could be an important therapeutic adjunct for the prevention of transplant rejection. Utilizing techniques of gene transfer, we previously demonstrated that plasmid mediated transfer of TGF-β1 could prolong allograft survival. In this study, we demonstrate that TGF-β1 gene transfer-induced immunosuppression is localized only to the area of the graft Prolongation of graft survival is associated with inhibition of donor-specific cytotoxic T cell and interleukin-2 (IL-2) producing helper T cell function in graft-infiltrating cells, the priming of TH0 cells, and the conversion of primed TH1 cells to activated cells without the participation of TH2 suppressors. These data demonstrate that gene transfer of plasmid DNA encoding TGF-β1 in vivo suppresses local T cell immunity, which prolongs allograft survival.