B7-H1 Expression Is Required for Human Endometrial Regenerative Cells in the Prevention of Transplant Vasculopathy in Mice.

Kui Ye,Grace Wang,Xiang Li,Hao Wang,Baoren Zhang,Xiaoxi Xu,Xu Lan,Yiming Zhao

doi:10.1155/2018/2405698

Abstract

Vasculopathy is one of the primary pathological changes in chronic rejection of vascularized allograft transplantation. Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells with immunosuppressive effect. B7-H1 is a negative costimulator that mediates active immune suppression. The aim of this study was to investigate the requirement of B7-H1 in the immunoregulation of ERCs in preventing transplant vasculopathy of aorta allografts. The results showed that B7-H1 expression on ERCs was upregulated by IFN-γ in a dose-dependent manner and it was required for ERCs to inhibit the proliferation of peripheral blood mononuclear cells (PBMCs) in vitro. ERCs could alleviate transplant vasculopathy, as the intimal growth of transplanted aorta was limited, and the preventive effects were correlated with an increase in the percentages of CD11c+MHC class IIlowCD86low dendritic cells, CD68+CD206+ macrophages, and CD4+CD25+Foxp3+ T cells, as well as a decrease in the percentages of CD68+ macrophages, CD3+CD4+ T cells, CD3+CD8+ T cells, and donor-reactive IgM and IgG antibodies. Moreover, overexpression of B7-H1 by IFN-γ can promote the immunosuppressive effect of ERCs. These results suggest that overexpression of B7-H1 stimulated by IFN-γ is required for ERCs to prevent the transplant vasculopathy, and this study provides a theoretical basis for the future clinical use of human ERCs.

Highlights

With the rapid development of surgical procedures, organ and cell isolation, and preservation techniques, as well as the advance of transplant immunology, organ transplantation has become an effective and routine treatment for end-stage diseases
The results indicated that Endometrial regenerative cells (ERCs) could decrease the generation of circulation antidonor antibodies and B7-H1 expressed on ERCs was critical in this process
On the basis of previous studies of ERCs, through upregulating B7-H1 by IFN-γ and neutralization of B7-H1 by anti-B7-H1 monoclonal antibody (mAb), the present study has demonstrated that B7-H1 plays a critical role in enhancing the immunosuppressive effects of ERCs both in vitro coculture cell proliferation and in vivo transplant vasculopathy

Summary

Introduction

With the rapid development of surgical procedures, organ and cell isolation, and preservation techniques, as well as the advance of transplant immunology, organ transplantation has become an effective and routine treatment for end-stage diseases. Due to the progression of allograft immunology, some new types of immunosuppressive agents and therapy are used and that have prevented or reversed acute allograft rejection effectively in the past 20 years, which lead to the short-term (1-year) allograft survival time of 88–95% [1]. These immunosuppressive therapies are not effective for the prevention and treatment of chronic rejection caused by transplant vasculopathy. The transplant vasculopathy in chronic rejection has become a major obstacle to long-term survival of transplanted organs, and an effective treatment is urgently needed [4]

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