Adoptive transfusion of tolerant dendritic cells prolong the survival of renal allografts: A systematic review

Abstract

Objective: The aim of this study was to systematically review the effects of transfusing Tol-DCs induced by different methods on renal transplantation and survival time. Method: PubMed and EMbase were searched for relevant articles from inception to July 20th, 2013. Renal allograft survival time was regarded as the endpoint outcome. The effects of Tol-DCs on renal transplantation were evaluated semi-quantitatively. Results: Sixteen articles were included. There were three sources of Tol-DCs, including bone marrow, spleen, and thoracic duct lymph node. Rats were administrated cells intravenously and 83% of mice through the portal vein. Four subtypes of bone marrow Tol-DCs enhanced renal allograft time: immature DCs enhanced allograft survival 4.9-fold in rats and 2.0-fold in mice, gene modified DCs enhanced allograft survival 4.4-fold in rats and 2.2-fold in mice, and drug and cytokine induced enhanced allograft survival 2.9-fold and 2.7-fold, respectively, in rats. Tol-DCs from the spleen and thoracic duct lymph nodes prolonged allograft survival 2.7-fold and 1.8-fold, respectively, in rats. 1-2×106 doses of Tol-DCs extended the survival time of rats following renal transplantation. The key mechanisms by which Tol-DCs enhance allograft and overall survival included: (i) inducing T-cell hyporeactivity; (ii) reducing the effects of cytotoxic lymphocytes; and (iii) inducing Th2 differentiation. Conclusion: Bone marrow Tol-DCs can extend allograft survival and induce immune tolerance in fully MHC-mismatched renal transplantation in rats and mice. The effects of imDCs and gene modified Tol-DCs in mice are less marked. In conclusion, a single-injection of 1-2×106 doses of bone marrow Tol-DCs (i.v.), in combination with an immune-suppressor, a co-stimulator, and accessory cells can significantly extend renal allograft survival. © 2013 Chinese Cochrane Center, West China Hospital of Sichuan University and Wiley Publishing Asia Pty Ltd.