Establishmentof a strategy to regulate alloreactive T cells by CD14^+monocyte-derived endothelial-like cells for applying in organ transplantation

CD14^单核细胞源性内皮样细胞调控同种异体反应性T细胞策略的建立及其在器官移植中的应用

• 批准号: 20790931
• 负责人: TANAKA Yuka
• 金额: $ 2.66万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790931/
• 关键词: 臓器移植; 免疫寛容; 内皮細胞

We have established a strategy to inhibit alloreactive T cells without nonspecific immunosuppressants by using immune-regulatory endothelial-like cells (ELCs) derived from peripheral blood CD14^+ monocytes. We have also attempted to establish an in vivo mouse model to investigate the strategy to regulate alloreactive T cells (i.e. liver endothelia-chimeric Rag-2/γ-chain double knockout mice reconstructed with syngeneic T cells). The ELCs regenerated from peripheral blood CD14+ monocytes expressed MHC class II, CD80 and CD86 together with PDL-1 and ILT-3 (inhibitory molecules against T cells). Adding the stimulator-type ELCs into the culture of mixed reaction assay resulted in the significant inhibition of T cell proliferation in the stimulator-specific fashion. These findings suggest that adoptive transfer with the ELCs regenerated from donor peripheral blood CD14^+ monocytes specifically induces tolerance among alloreactive T cells in organ transplantation.

我们已经建立了一种不使用非特异性免疫抑制剂，通过使用外周血CD 14 ^+单核细胞来源的免疫调节性内皮样细胞（ELC）来抑制同种异体反应性T细胞的策略。我们还尝试建立体内小鼠模型以研究调节同种异体反应性T细胞的策略（即用同基因T细胞重建的肝内皮嵌合Rag-2/γ-链双敲除小鼠）。从外周血CD 14+单核细胞再生的ELC表达MHC II类、CD 80和CD 86以及PDL-1和ILT-3（针对T细胞的抑制分子）。在混合反应培养物中加入刺激因子型ELC，可显著抑制T细胞的增殖，且具有刺激因子特异性。这些发现表明，过继转移供体外周血CD 14 ^+单核细胞再生的ELC可特异性诱导器官移植中同种异体反应性T细胞的耐受。

项目成果

Immunological property of antibodies against N-glycolylneuraminic acid epitopes in cytidine monophospho-N-acetylneuraminic acid hydroxylase-deficient mice.

胞苷单磷酸-N-乙酰神经氨酸羟化酶缺陷小鼠中针对 N-羟乙酰神经氨酸表位的抗体的免疫学特性。

• 发表时间: 2009
• 期刊: Journal of Immunology 184
• 作者: Tahara H;Ide K;Basnet N.B;Ohdan H;et al.
• 通讯作者: et al.

当院における肝移植後の免疫寛容をめざした試み～肝類洞内皮細胞の抗原特異的免疫寛容誘導能～

我院肝移植后实现免疫耐受的尝试-肝窦内皮细胞抗原特异性免疫耐受诱导能力-

• 发表时间: 2009
• 作者: Yuka Tanaka;Hirotaka Tashiro;Hideki Ohdan;番匠谷将孝
• 通讯作者: 番匠谷将孝

Determination of the precursor frequency and the reaction intensity of xenoreactive human T lymphocytes

• DOI: 10.1111/j.1399-3089.2010.00575.x
• 发表时间: 2010-05-01
• 期刊: XENOTRANSPLANTATION
• 影响因子: 3.9
• 作者: Tahara, Hiroyuki;Ide, Kentaro;Ohdan, Hideki
• 通讯作者: Ohdan, Hideki

Optimization of immunosup pressive the rapy on the basis of immune monitoringby a multipara metric mixed lymphocy tereaction assay reduces in fectiouscomp lications and mortality inliving-donor liver transplantation

通过多参数混合淋巴细胞反应测定进行免疫监测，优化免疫抑制治疗可降低活体肝移植的感染性并发症和死亡率

• 发表时间: 2010
• 作者: Yuka Tanaka;Hirotaka Tashiro;HidekiOhdan
• 通讯作者: HidekiOhdan

肝類洞内皮細胞の抗原特異的免疫寛容誘導能の解析

肝窦内皮细胞诱导抗原特异性免疫耐受能力分析

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