Shirwan H, Cajulis E, Makowka L, Cramer D V
Department of Surgery, Cedars-Sinai Research Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Transplantation. 1995 Jun 27;59(12):1709-14. doi: 10.1097/00007890-199506270-00012.
We have previously demonstrated that the immune response to cardiac allografts in the ACI-to-LEW rat strain combination involves a limited use of the TCR V beta gene repertoire. In the present study we analyzed the expression of V beta genes by T cells infiltrating kidney and liver allografts to test whether a limited use of the T cell receptor (TCR) repertoire is a common denominator for immune responses to allografts. Graft-infiltrating lymphocytes (GIL) were isolated from allografts on different days after transplantation and analyzed for the expression of V beta genes using a semi-quantitative polymerase chain reaction (PCR) without manipulations in tissue culture. We detected a limited expression of the V beta gene repertoire in fresh GIL harvested from both kidney and liver allografts early in graft rejection. The level of TCR repertoire usage, however, was influenced by the type of graft. The rejection of heart and kidney allografts was associated with more limited use of the V beta gene repertoire when compared with that seen for the rejection of liver allografts. The limited use of the V beta gene repertoire was only apparent when analyzed early in graft rejection; as the rejection reaction progressed T cells using a more diverse V beta repertoire infiltrated the graft. The limited use of TCR repertoire of the early T cell response to allografts may provide the opportunity to therapeutically disrupt the rejection reaction by targeting selected T cell populations for elimination at the time of organ transplantation.
我们之前已经证明，在ACI到LEW大鼠品系组合中，对心脏同种异体移植物的免疫反应涉及TCR Vβ基因库的有限使用。在本研究中，我们分析了浸润肾脏和肝脏同种异体移植物的T细胞中Vβ基因的表达，以测试T细胞受体（TCR）库的有限使用是否是同种异体移植物免疫反应的共同特征。移植后不同时间从同种异体移植物中分离出移植物浸润淋巴细胞（GIL），并使用半定量聚合酶链反应（PCR）分析Vβ基因的表达，无需在组织培养中进行操作。我们在移植早期从肾脏和肝脏同种异体移植物收获的新鲜GIL中检测到Vβ基因库的有限表达。然而，TCR库的使用水平受移植物类型的影响。与肝脏同种异体移植物排斥反应相比，心脏和肾脏同种异体移植物的排斥反应与Vβ基因库的使用更有限有关。Vβ基因库的有限使用仅在移植早期分析时明显；随着排斥反应的进展，使用更多样化Vβ库的T细胞浸润移植物。同种异体移植物早期T细胞反应中TCR库的有限使用可能为在器官移植时通过靶向选定的T细胞群体进行消除来治疗性破坏排斥反应提供机会。
