Transforming growth factor beta-induced connective tissue growth factor and chronic allograft rejection

Late loss of allograft function is primarily attributed to chronic rejection (CR). There are no effective treatments for CR and the underlying cause of the disease is unknown. This study compared events that occurred within cardiac allografts placed in mice that received either anti-CD4 therapy and develop CR or anti-CD40L therapy and do not develop CR. Both TGFP and connective tissue growth factor (CTGF), which is induced by TGFO, were expressed in grafts with CR but were not expressed in grafts without CR. TGFO transfection of allografts in anti-CD40L-treated recipients resulted in CTGF expression and CR. However, TGFP transfection of syngeneic grafts did not result in CTGF expression or CR. These data indicate that TGFP alone is insufficient to induce CR and that CTGF is required. Further, antigenic stimulation is required for TGFP induction of CTGF. Thus, CTGF may serve as a therapeutic target for CR.