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

我们在大鼠肺移植模型上研究了T细胞受体V-β基因在移植物浸润性淋巴细胞中的表达模式。在Brown挪威(BN，RT1)和Lewis(LEW，RT1)大鼠肺移植中，未加免疫抑制剂的大鼠肺移植后7d内发生急性排斥反应。从BN到LEW的同种异体肺移植术后(移植后第2天和第3天，静脉注射环孢素A，25 mg/kg)无限期地接受环孢素A(CsA)治疗，但这些肺移植后经常出现晚期呼吸道改变，如肉芽组织和粘膜下纤维化伴淋巴细胞浸润性改变。在接受相同免疫抑制治疗的同种异体肺移植中，未观察到这些晚期的气道改变。在这些实验模型中，我们评估了同种异体肺移植中TCR的表达，以确定排斥移植肺中的T细胞是否使用了限制性的V-β元件。V-bet…的半定量聚合酶链式反应分析在急性排斥肺中，V-β基因的表达模式与同种异体移植肺不同。在急性排斥肺中，V-β5和V-β8基因均有较强的表达。慢性排斥30天时，V-β9基因的表达强于30天时的肺。30天时，CsA处理的同种异体移植肺的血管周围和支气管周围细胞浸润情况与急性排斥反应血管期3天时相似。CsA处理的移植肺在移植后30d达到高峰，以后逐渐减少。我们推测同种异体排斥反应与移植物浸润性淋巴细胞对V-β5和V-β8 TCR的使用受到限制有关。30d同种异体肺组织中V-β9TCR的过度表达可能与排斥反应的抑制机制有关。较少

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