Oral Tolerance Induction by Type V Collagen in Lung Transplantation

肺移植中 V 型胶原诱导口服耐受

• 批准号: 15591466
• 负责人: SEKINE Yasuo
• 金额: $ 2.24万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591466/
• 关键词: Lung Transplantation; Oral Tolerance; Type V Collagen; Allograft Rejection; 肺移殖

Objective : Lung allograft rejection involves an immune response to type V collagen [col(V)]. Oral tolerance induced by col(V) abrogates delayed type hypersensitivity (DTH) responses to donor antigens, and prevented acute and chronic lung allograft rejection. These data suggest that col(V)-induced tolerance might have stimulated regulatory T cells that suppress rejection responses. The purpose of the current study was to determine if col(V) oral tolerance induced regulatory T cells, and to determine the mechanism of immune suppression induced by these cells utilizing F344 lung allografts (RT1^<lv1> for orthotopic transplantation into WKY (RT1^1) rat recipients.Materials and Methods : We utilized our recently described model of col(V)-induced oral tolerance to lung allografts in which feeding col(V) to WKY rats prior to transplantation induced tolerance to F344 lung allografts. CD4+ and CD8+ T cells were purified from spleens of different groups of WKY rats including tolerant rats and used for adoptive transfer studies. DTH responses and rejection pathology were assessed in different groups of adoptively transferred animals.Results : Data showed that adoptive transfer of CD4+, but not CD8+, T cells from tolerant rats to untreated allograft recipients abrogated DTH responses to donor antigens, and prevented acute and chronic lung allograft rejection. MLR's revealed that CD4+ T cells from tolerant rats produced TGF-β constitutively and in response to alloantigen. Finally, anti- TGF-β antibodies recovered DTH responses suppressed by adoptive transfer of "tolerant" CD4+ T cells.Conclusion : We conclude that col(V)-induced oral tolerance results in activity of regulatory CD4+ T cells that suppress alloreactivity by production of TGF-β.

目的：肺同种异体移植排斥反应涉及对V型胶原的免疫反应[col(V)]。col(V)诱导的口服耐受消除了对供体抗原的延迟型超敏反应（DTH），并防止急性和慢性肺同种异体移植排斥反应。这些数据表明，col(V)诱导的耐受性可能刺激了抑制排斥反应的调节性T细胞。本研究的目的是确定col(V)口服耐受是否诱导调节性T细胞，并确定这些细胞诱导的免疫抑制机制，利用F344肺同种异体移植物（RT1^<lv1>）原位移植到WKY （RT1^1）大鼠受体中。材料和方法：我们利用我们最近描述的col(V)诱导的肺同种异体移植耐受模型，在移植前给WKY大鼠喂食col(V)诱导对F344肺同种异体移植的耐受。从包括耐受大鼠在内的不同组WKY大鼠脾脏中纯化CD4+和CD8+ T细胞，用于过继性转移研究。对不同组动物的DTH反应和排斥病理进行了评估。结果：数据显示，耐受大鼠的CD4+（而非CD8+） T细胞过继转移到未治疗的同种异体移植受体，消除了对供体抗原的DTH反应，并预防了急性和慢性同种异体肺移植排斥反应。MLR结果显示，耐受大鼠的CD4+ T细胞组成性地对同种异体抗原产生TGF-β。最后，抗TGF-β抗体恢复了被“耐受”CD4+ T细胞过继转移抑制的DTH反应。结论：col(V)诱导的口服耐受性导致调节性CD4+ T细胞活性，通过TGF-β的产生抑制同种异体反应性。

项目成果

Type V collagen-induced oral tolerance to lung allografts is mediated by CD4+ regulatory T cells

V型胶原诱导的肺同种异体移植口服耐受是由CD4调节性T细胞介导的

• 发表时间: 2004
• 期刊: Japanese Journal of Transplantation 39(4)
• 作者: Kazuhiro Yasufuku

Comparison of surgical procedures for vascular and airway anastomosis that utilize a modified non-suture external cuff technique for experimental lung transplantation in rats

使用改良的非缝合外袖带技术进行大鼠实验性肺移植的血管和气道吻合手术程序的比较

• 发表时间: 2004
• 期刊: Journal of Heart and Lung Transplantation 23・7
• 作者: Azuma K;Sasada T;Takedatsu H;Shomura H;Koga M;Maeda Y;Yao A;Hirai T;Takabayashi A;Shichijo S;Itoh K.;Sugio K;安福 和弘;Oyama T;Teruaki Mizobuchi
• 通讯作者: Teruaki Mizobuchi

Comparison of surgical procedures for vascular and airway anastomoses that utilize a "modified" non-suture external cuff technique for experimental lung transplantation in rats

• DOI: 10.1016/j.healun.2003.06.009
• 发表时间: 2004-07-01
• 期刊: JOURNAL OF HEART AND LUNG TRANSPLANTATION
• 影响因子: 8.9
• 作者: Mizobuchi, T;Sekine, Y;Wilkes, DS
• 通讯作者: Wilkes, DS

肺移植におけるV型コラーゲン経口寛容の機序 -CD4+調節性T細胞の役割

V型胶原口服耐受在肺移植中的机制——CD4+调节性T细胞的作用

• 发表时间: 2004
• 期刊: 移植(日本移植学会雑誌) 39・4
• 作者: Azuma K;Sasada T;Takedatsu H;Shomura H;Koga M;Maeda Y;Yao A;Hirai T;Takabayashi A;Shichijo S;Itoh K.;Sugio K;安福 和弘
• 通讯作者: 安福 和弘

肺移植実験モデル:ラット同種間同所性左肺移植技術改良の試み

肺移植实验模型：大鼠同种异体原位左肺移植技术的尝试

• 发表时间: 2004
• 期刊: 千葉医学雑誌 80・2
• 作者: H Fujita;S Sueyoshi;T Tanaka;et al.;Oyama T;溝渕 輝明
• 通讯作者: 溝渕 輝明