IMMUNOSUPPRESSION WITH ANTI-T CELL RECEPTOR V-BETA ANTIBODY IN LUNG TRANSPLANTATON

肺移植中抗 T 细胞受体 V-β 抗体的免疫抑制

• 批准号: 09671383
• 负责人: SAKIYAMA Shoji
• 金额: $ 2.05万
• 依托单位: The university of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671383/
• 关键词: lung transplantation; rat; TCR; TCR V-BETA; acute rejection; chronic rejection; immunosuppression; TCRVbeta; TCRV-beta

We investigated the expression pattern of T cell receptor V-beta gene in graft infiltrating lymphocytes on the rat lung transplantation models. In the Brown Norway (BN, RT1) to Lewis (LEW, RT1) rat lung transplantation with no immunosuppresant, garafted lungs were acutely rejected within 7days after transplantation. Although lung allografts form BN to LEW were indefinitely accepted with a short course cyclosporine(CsA) administration after transplantation (on day 2 and 3 after transplantation , 25mg/kg, i.m.), late airway changes, such as granulation and submucosal fibrosis with infiltrating lymphocytes, were frequently observed in these lung allografts. These late airway changes were not observed in lung isografts treated with the same immunosuppressive treatment.With these experimental models, TCR expression were evaluated in lung allografts to determine whether T cells infiltrating rejecting lung allografts employed restricted V-beta elements. Semi-quantitative PCR analysis of V-bet … More a gene usage was performed using V-beta specific primers.The pattern of expression of V-beta gene in acutely rejecting lungs was different form that of isografted lungs. In acutely rejecting lungs, V-beta 5 and V-beta 8 gene were strongly expressed. In chronically rejecting lungs on day 30, V-beta 9 gene expression was stronger than that in lungs on day 30.On day 30 after transplantation, the allografts treated with CsA showed perivascular and peribronchial cellular infiltration similar to that found on day 3 in the vascular phase of acute rejection. The peak of the number of the infiltrating cells in grafted lungs with CsA treated was shown on day 30 after transplantation, after that, the number of the infiltrating cells was gradualy reduced.We postulated that allograft rejection is associated with restricted V-beta 5 and V-beta 8 TCR usage by graft infiltrating lymphocytes. Over expression of V-beta 9 TCR in allografted lungs on day 30 may related to suppressive mechanism for graft rejection. Less

本研究观察了大鼠肺移植模型中T细胞受体V β基因在移植物浸润淋巴细胞中的表达情况。在Brown Norway（BN，RT 1）至刘易斯（LEW，RT 1）大鼠肺移植中，未使用免疫抑制剂，移植后7天内出现急性排斥反应。尽管移植后短期给予环孢素（CsA）（移植后第2天和第3天，25 mg/kg，i.m.），从BN到LEW的肺同种异体移植物被无限期接受，在这些肺同种异体移植物中经常观察到晚期气道变化，例如肉芽形成和粘膜下纤维化以及浸润的淋巴细胞。这些晚期气道变化在用相同的免疫抑制剂治疗的肺同种异体移植物中没有观察到，用这些实验模型，评估肺同种异体移植物中TCR的表达，以确定T细胞浸润排斥肺同种异体移植物是否采用限制性V-β元件。V-bet的半定量PCR分析 ...更多信息 用V-β特异性引物进行基因筛选，发现急性排斥肺中V-β基因的表达模式与同种移植肺不同。在急性排斥肺中，V-β 5和V-β 8基因强表达。慢性排斥组肺组织中V-β 9基因表达强于慢性排斥组肺组织。CsA处理组肺组织中V-β 9基因表达强于慢性排斥组肺组织。CsA处理的移植肺中浸润细胞数在移植后30天达高峰，此后逐渐减少，我们推测移植排斥反应与移植肺浸润淋巴细胞对V-β 5和V-β 8 TCR的限制性利用有关。移植肺内V β 9 TCR在第30天的过度表达可能与移植排斥反应的抑制机制有关。少

项目成果

宇山 正: "ラット肺移植" Organ Biology. vol.4(2). 37-41 (1997)

Tadashi Uyama：“大鼠肺移植”器官生物学第 4 卷（2）（1997 年）。

Tadashi Uyama: "Bronchus-associated lymphord tissue is targeted and damaged by recipient lymphocytes in ling-term-surviving rat lung allograft" Transplant Proc. vol.29. 2617-2618 (1997)

Tadashi Uyama：“在长期存活的大鼠同种异体肺移植物中，支气管相关淋巴组织被受体淋巴细胞靶向并损伤”移植程序。