Adoptive infusion of tolerance dendritic cells prolongs survival of small intestine allografts in rats: systematic review and meta-analysis

J Evid Based Med. 2013 Aug;6(3):185-96. doi: 10.1111/jebm.12050.

Abstract

Background: Postoperative infections and rejection are the main limiting factors of small intestine allograft survival. In this study, we performed a systematic review and meta-analysis to review rat small intestine allograft survival following infusion of tolerance dendritic cells (Tol-DCs) induced by different methods.

Methods: Relevant publications were searched from PubMed database and EMbase database. Meta-analysis was performed using RevMan 5.0 software. We chose allograft survival, mixed leukocyte reaction, Th1/Th2 differentiation, Treg induction, and cytotoxic T lymphocyte activity as the outcomes by which to examine possible mechanisms that promote survival.

Results: Eleven suitable articles were identified and assessed. Tol-DCs induced by four methods all prolonged allograft survival. The difference in survival time between the Tol-DC group and the control group was indicated by SMD as follows: drug intervention (SMD = 3.02, 95% CI 1.16 to 4.88, P = 0.001), gene modification (SMD = 2.43, 95% CI 1.77 to 3.10, P < 0.00001), imDC (SMD = 1.76, 95% CI 0.90 to 2.62, P < 0.0001), cytokine induction (SMD = 1.68, 95% CI 0.40 to 2.96, P = 0.01). Tol-DCs were also synergistic with immunosuppressive drugs or costimulation inhibitors, but no immune tolerance was observed. A single-dose intravenous injection of 5×10(6) to 6×10(6) Tol-DCs showed the highest allograft survival. Possible mechanisms included donor-specific T-cell hyporesponsiveness and Th2 differentiation.

Conclusions: Our results demonstrated that Tol-DCs induced by four methods prolong rat small intestine allograft survival. Intravenous infusion of 5×10(6) to 6×10(6) Tol-DCs was the optimum dose in rat small intestine transplantation. Immunosuppressive or costimulatory blockade was synergistic with Tol-DC on graft survival. Additional high-quality studies with larger sample sizes are needed to better investigate small intestinal graft longer term survival.

Keywords: Adoptive transfusion; animal experiment; meta‐analysis; small intestine allograft; tolerogenic dendritic cells.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adoptive Transfer*
  • Animals
  • Dendritic Cells / immunology*
  • Dose-Response Relationship, Immunologic
  • Graft Survival / immunology*
  • Immune Tolerance*
  • Intestine, Small / transplantation*
  • Publication Bias
  • Rats