Development of novel cellular therapy for T cell mediated rejection via direct and indirect pathway using regulatory liver sinusoidal endothelial cells (LSEC) in transplantation

在移植中使用调节性肝窦内皮细胞 (LSEC) 通过直接和间接途径开发针对 T 细胞介导的排斥反应的新型细胞疗法

• 批准号: 21890155
• 负责人: ONOE Takashi
• 金额: $ 1.7万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21890155/
• 关键词: 肝移植; 免疫寛容; 移植免疫; 類洞内皮細胞; キメラ; PD-L1

We have shown that liver sinusoidal endothelial cells (LSEC) has antigen specific immune-suppressive potential in vitro. In this study, we evaluated the possibility that adoptive transfer of isolated allogeneic LSECs induce immune-tolerance in vivo mouse model. Allogeneic BALB/cA LSECs were intraportally injected into immunodeficient RAG2/gc double-knockout (DKO) mice. After orthotopic allogeneic LSEC engraftment, engrafted LSECs expressed PD-L1 molecule. DKO mice were immune-reconstituted using C57BL/6 syngeneic splenocytes. After immune reconstitution, mixed lymphocyte reaction revealed specific inhibition of host alloreactive T-cell proliferation. Furthermore, allogeneic LSEC engraftment significantly prolonged subsequently grafted cognate allogeneic heart survival in DKO mice immune-reconstituted with syngeneic bone marrow transplantation. In conclusion, murine LSECs are capable of suppressing T cells with specificity cognate to LSECs in an in vivo model.

我们已经证明肝窦内皮细胞(LSEC)在体外具有抗原特异性免疫抑制潜能。在这项研究中，我们评估了过继转移分离的同种异体LSECs在活体小鼠模型中诱导免疫耐受的可能性。将同种异体BALB/CA LSECs注射到免疫缺陷RAG2/GC双基因敲除(DKO)小鼠体内。同种异体LSEC原位移植后，LSEC表达PD-L1分子。用C57BL/6同基因脾细胞对dKO小鼠进行免疫重建。免疫重建后，混合淋巴细胞反应表现出对宿主同种反应性T细胞增殖的特异性抑制。此外，同种异体LSEC移植显著延长了同基因骨髓移植免疫重组的DKO小鼠随后移植的同种异体心脏的存活时间。综上所述，在体内模型中，小鼠LSECs能够抑制与LSECs特异性同源的T细胞。

项目成果

Distinct requirements for achievement of allotolerance versus reversal of autoimmunity via nonmyeloablative mixed chimerism induction in NOD mice.

在 NOD 小鼠中通过非清髓性混合嵌合诱导实现同种异体耐受与逆转自身免疫的不同要求。

• 发表时间: 2010
• 期刊: Transplantation 89(1)
• 作者: Nikolic B;Onoe T;et al.
• 通讯作者: et al.

Advantageous effect of a continuous injection of PGE1 via the portal vein for small-for size graft in adult-to-adult living donor liver transplantation

门静脉持续注射PGE1对小体积移植物在成人活体肝移植中的有利作用

• 发表时间: 2010
• 作者: 番匠谷将孝;尾上隆司;尾上隆司;尾上隆司
• 通讯作者: 尾上隆司

Evidence for tolerizing allo reactive T cell by LSECs in a liver endothelium repopulation in vivo model

LSEC 在体内肝内皮再生模型中耐受同种异体反应性 T 细胞的证据

• 发表时间: 2009
• 作者: Banshoudani M;Onoe T;et al.;番匠谷将孝
• 通讯作者: 番匠谷将孝

肝類洞内皮細胞のアロ応答性T細胞制御能:in vivoモデルでの解明

肝窦内皮细胞控制同种异体反应性 T 细胞的能力：体内模型的阐明

• 发表时间: 2010
• 作者: 番匠谷将孝;尾上隆司
• 通讯作者: 尾上隆司

Advantageous effect of a continuous injection of PGE1 via the portal vein for small-for-size graft in adult-to-adult living donor liver transplantation

门静脉持续注射PGE1在小体积移植物成人-成人活体肝移植中的优势

• 发表时间: 2010
• 作者: 番匠谷将孝;尾上隆司;尾上隆司
• 通讯作者: 尾上隆司