Induction of allograft tolerance by adoptive transfer of donor B cells: an immune regulatory strategy for transplantation using MHC-matched iPS cells
Induction of allograft tolerance by adoptive transfer of donor B cells: an immune regulatory strategy for transplantation using MHC-matched iPS cells
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DOI：
10.1093/intimm/dxad008
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发表时间：
2023-04-13
影响因子：
4.4
通讯作者：
Seino，Ken-ichiro
中科院分区：
文献类型：
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作者：
Murata，Tomoki;Otsuka，Ryo;Seino，Ken-ichiro
对于使用诱导多能干细胞（iPSC）的细胞或组织移植，从时间和经济成本的观点来看，正在考虑使用同种异体干细胞。免疫调节是异基因移植成功的关键问题之一。为了降低排斥的风险，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，我们已经表明，即使MHC的影响被减轻，轻微的抗原诱导的排斥反应也是不可忽略的。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应答。然而，DST是否可以控制基于iPSC的移植中的免疫应答尚不清楚。在这项研究中，使用小鼠皮肤移植模型，我们证明了输注供体脾细胞可以促进MHC匹配但轻微抗原不匹配条件下的同种异体移植物耐受。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细胞的给药诱导受体T细胞的无反应性，但不删除，这表明耐受性是在外周诱导的。供体B细胞输注诱导同种异体iPSC植入。这些结果首次表明，使用供体B细胞的DST可以诱导对同种异体iPSC衍生移植物的耐受。
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.