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

在大鼠肺移植模型上研究T细胞受体v - β基因在移植物浸润淋巴细胞中的表达谱。在未使用免疫抑制剂的Brown Norway （BN, RT1）对Lewis （LEW, RT1）大鼠肺移植中，移植肺在移植后7天内出现急性排斥反应。虽然移植后给予短疗程环孢素（CsA）（移植后第2天和第3天，25mg/kg, i.m.m），可以无限期接受从BN到LEW的肺同种异体移植物，但在这些肺同种异体移植物中经常观察到晚期气道改变，如肉芽肿和粘膜下纤维化伴淋巴细胞浸润。在接受相同免疫抑制治疗的肺同种移植物中未观察到这些晚期气道改变。通过这些实验模型，评估TCR在肺同种异体移植物中的表达，以确定T细胞浸润排斥肺同种异体移植物是否使用限制性v - β元素。利用v - β特异性引物对v - β基因进行半定量PCR分析。v - β基因在急性排斥肺中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基因强烈表达。在第30天的慢性排斥肺中，v - β 9基因表达强于第30天的肺。移植后第30天，经CsA处理的同种异体移植物血管周围和支气管周围细胞浸润，与急性排斥反应血管期第3天相似。经CsA处理的移植肺浸润细胞数量在移植后第30天达到高峰，此后浸润细胞数量逐渐减少。我们假设同种异体移植排斥反应与移植物浸润淋巴细胞限制v - β 5和v - β 8 TCR的使用有关。同种异体肺移植第30天v - β 9 TCR的过度表达可能与移植排斥反应的抑制机制有关。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