Cotransfection with IL-10 and TGF-beta1 into immature dendritic cells enhances immune tolerance in a rat liver transplantation model

摘要

Dendritic cells transfected with interleukin (IL)-10 and transforming growth factor-beta1 (TGF-beta1) enhance T cell immunity and tolerance. However, no quantitative studies have investigated the sup-pressive functions of immature dendritic cells (imDC) cotransfected with IL-10 and TGF-beta1. The effects of imDC cotransfected with IL-10 and TGF-beta1 (IL-10-TGF-beta1-imDC) on immune tolerance induction in a rat transplantation model were investigated. In addition, effects of IL-10-TGF-pi-imDC relative to IL-10-trans-fected imDC (IL-10-imDC) and TGF-beta1-transfected imDC (TGF-beta1-imDC) were compared. The infusion of IL-10-TGF-beta1-imDC into recipients prolonged liver graft survival, which was sustained for >90 days. IL-12 serum levels decreased, whereas alanine transaminase and total bilirubin slightly increased in rats infused with IL-10-TGF-beta1-imDC compared with the IL-10-imDC and TGF-beta1-imDC groups. Furthermore, a higher percentage of terminal transferase-mediated UTP nick end-labeling-positive cells was observed, and histological analysis of the allografts indicated a rejection activity index of mild acute rejection. Our results suggest infusion of IL-10 and TGF-beta1 cotransfected imDC induces alloan-tigen-specific T cell hyporesponsiveness, inhibits antigen-specific immunological responses to liver allografts, prolongs liver allo-graft survival, and enhances the immune tolerance. This approach may provide a promising alternative for enhancing donor-specific tolerance during liver transplantation.