Induction of allograft tolerance by adoptive transfer of donor B cells: an immune regulatory strategy for transplantation using MHC-matched iPS cells.

IF 4.8 4区 医学 Q2 IMMUNOLOGY
Tomoki Murata, Ryo Otsuka, Airi Sasaki, Tomoki Kamatani, Haruka Wada, Hisashi Yamakawa, Yoshinori Hasegawa, Ken-Ichiro Seino
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引用次数: 0

Abstract

For cellular or tissue transplantation using induced pluripotent stem cells (iPSCs), from the viewpoint of time and economic cost, the use of allogeneic ones is being considered. Immune regulation is one of the key issues in successful allogeneic transplantation. To reduce the risk of rejection, several attempts have been reported to eliminate effects of the major histocompatibility complex (MHC) on the iPSC-derived grafts. On the other hand, we have shown that minor antigen-induced rejection is not negligible even when the MHC's impact is mitigated. In organ transplantation, it is known that donor-specific transfusion (DST) can specifically control immune responses to the donor. However, whether DST could control the immune response in iPSC-based transplantation was not clarified. In this study, using a mouse skin transplantation model, we demonstrate that infusion of donor splenocytes can promote allograft tolerance in the MHC-matched but minor antigen-mismatched conditions. When narrowing down the cell types, we found that infusion of isolated splenic B cells was sufficient to control rejection. As a mechanism, the administration of donor B cells induced unresponsiveness but not deletion in recipient T cells, suggesting that the tolerance was induced in the periphery. The donor B cell transfusion induced allogeneic iPSC engraftment. These results suggest for the first time a possibility that DST using donor B cells could induce tolerance against allogeneic iPSC-derived grafts.

供体B细胞过继移植诱导同种异体移植物耐受:mhc匹配iPS细胞移植的免疫调节策略
对于使用诱导多能干细胞(iPSCs)进行细胞或组织移植,从时间和经济成本的角度考虑,正在考虑使用同种异体干细胞。免疫调节是同种异体移植成功的关键问题之一。为了降低排斥反应的风险,已经报道了几种尝试来消除主要组织相容性复合体(MHC)对ipsc衍生移植物的影响。另一方面,我们已经证明,即使MHC的影响减轻了,轻微的抗原诱导的排斥反应也是不可忽视的。在器官移植中,已知供体特异性输血(DST)可以特异性地控制对供体的免疫反应。然而,DST是否能控制ipsc移植的免疫反应尚不清楚。在这项研究中,我们使用小鼠皮肤移植模型,证明在mhc匹配但抗原不匹配的情况下,输注供体脾细胞可以促进同种异体移植物的耐受性。当缩小细胞类型时,我们发现输注分离的脾B细胞足以控制排斥反应。作为一种机制,供体B细胞在受体T细胞中诱导无反应性而非缺失,这表明耐受性是在外周诱导的。供体B细胞输注诱导异基因iPSC移植。这些结果首次表明,使用供体B细胞的DST可能诱导对异体ipsc衍生移植物的耐受性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
International immunology
International immunology 医学-免疫学
CiteScore
9.30
自引率
2.30%
发文量
51
审稿时长
6-12 weeks
期刊介绍: International Immunology is an online only (from Jan 2018) journal that publishes basic research and clinical studies from all areas of immunology and includes research conducted in laboratories throughout the world.
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