Adoptive Infusion of Tolerogenic Dendritic Cells Prolongs the Survival of Pancreatic Islet Allografts: a Systematic Review of 13 Mouse and Rat Studies

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Dec 29

PMID 23272217

Citations 8

Authors

Guixiang Sun

Juan Shan

Youping Li

Yanni Zhou

Yingjia Guo

Wenqiao Wu

Tong Yang

Mengjuan Xia

Li Feng

Affiliations

Soon will be listed here.

Abstract

Objective: The first Phase I study of autologous tolerogenic dendritic cells (Tol-DCs) in Type 1 diabetes (T1D) patients was recently completed. Pancreatic islet transplantation is an effective therapy for T1D, and infusion of Tol-DCs can control diabetes development while promoting graft survival. In this study, we aim to systematically review islet allograft survival following infusion of Tol-DCs induced by different methods, to better understand the mechanisms that mediate this process.

Methods: We searched PubMed and Embase (from inception to February 29(th), 2012) for relevant publications. Data were extracted and quality was assessed by two independent reviewers. We semiquantitatively analyzed the effects of Tol-DCs on islet allograft survival using mixed leukocyte reaction, Th1/Th2 differentiation, Treg induction, and cytotoxic T lymphocyte activity as mechanisms related-outcomes. We discussed the results with respect to possible mechanisms that promote survival.

Results: Thirteen articles were included. The effects of Tol-DCs induced by five methods on allograft survival were different. Survival by each method was prolonged as follows: allopeptide-pulsed Tol-DCs (42.14 ± 44 days), drug intervention (39 days), mesenchymal stem cell induction (23 days), genetic modification (8.99 ± 4.75 days), and other derivation (2.61 ± 6.98 days). The results indicate that Tol-DC dose and injection influenced graft survival. Single-dose injections of 10(4) Tol-DCs were the most effective for allograft survival, and multiple injections were not superior. Tol-DCs were also synergistic with immunosuppressive drugs or costimulation inhibitors. Possible mechanisms include donor specific T cell hyporesponsiveness, Th2 differentiation, Treg induction, cytotoxicity against allograft reduction, and chimerism induction.

Conclusions: Tol-DCs induced by five methods prolong MHC mismatched islet allograft survival to different degrees, but allopeptide-pulsed host DCs perform the best. Immunosuppressive or costimulatory blockade are synergistic with Tol-DC on graft survival. Multiple injections are not superior to single injection. Yet more rigorously designed studies with larger sample sizes are still needed in future.

Citing Articles

Advancements and Challenges in Immune Protection Strategies for Islet Transplantation.

Wang X, Zeng Z, Li D, Wang K, Zhang W, Yu Y J Diabetes. 2025; 17(1):e70048.

PMID: 39829227 PMC: 11744047. DOI: 10.1111/1753-0407.70048.

Local Immunomodulatory Strategies to Prevent Allo-Rejection in Transplantation of Insulin-Producing Cells.

Wang X, Brown N, Wang B, Shariati K, Wang K, Fuchs S Adv Sci (Weinh). 2021; 8(17):e2003708.

PMID: 34258870 PMC: 8425879. DOI: 10.1002/advs.202003708.

Impact of infection on transplantation tolerance.

Yu S, Su C, Luo X Immunol Rev. 2019; 292(1):243-263.

PMID: 31538351 PMC: 6961566. DOI: 10.1111/imr.12803.

Roles of Myeloid-Derived Suppressor Cell Subpopulations in Autoimmune Arthritis.

Li M, Zhu D, Wang T, Xia X, Tian J, Wang S Front Immunol. 2018; 9:2849.

PMID: 30564242 PMC: 6288996. DOI: 10.3389/fimmu.2018.02849.

Effects of Adoptive Transfer of Tolerogenic Dendritic Cells on Allograft Survival in Organ Transplantation Models: An Overview of Systematic Reviews.

Zhou Y, Shan J, Guo Y, Li S, Long D, Li Y J Immunol Res. 2016; 2016:5730674.

PMID: 27547767 PMC: 4980535. DOI: 10.1155/2016/5730674.

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