Shirwan H, Barwari L, Cramer D V
Transplantation Biology Research Laboratory, National Institute of Transplantation, Los Angeles, CA, USA.
Immunology. 1997 Apr;90(4):572-8. doi: 10.1046/j.1365-2567.1997.00187.x.
We have recently shown that T cells infiltrating cardiac allografts early in graft rejection use a limited T-cell receptor (TCR) V beta repertoire. In this study we tested whether this limited repertoire of V beta genes is important for graft rejection. A cell line, AL2-L3, was established from LEW lymphocytes infiltrating ACI heart allografts 2 days after transplantation. This cell line is composed of CD4+ T cells that primarily recognize the class II RTI.B major histocompatibility complex (MHC) molecule expressed by the donor graft. This cell line precipitated acute rejection of donor hearts with a median survival time (MST) of 10.5 days following adoptive transfer to sublethally irradiated LEW recipients. This rate of graft rejection was significantly (P < 0.0007) accelerated when compared with a MST of 60 days for allografts in irradiated control recipients. The AL2-L3-mediated acceleration of graft rejection was donor specific as WF third-party heart allografts were rejected with a delayed tempo (MST = 28.5 days). The V beta repertoire of this cell line was primarily restricted to the expression of V beta 4, 15 and 19 genes. The nucleotide sequence analysis of the beta-chain cDNAs from this cell line demonstrated that the restricted use of the V gene repertoire was not shared with the N, D and J regions. A wide variety of CDR3 loops and J beta genes were used in association with selected V beta genes. These data provide evidence for the role a restricted repertoire of V beta genes plays in cardiac allograft rejection in this model. The restricted usage of the V beta repertoire in an 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.
我们最近发现，在移植排斥反应早期浸润心脏同种异体移植物的T细胞使用有限的T细胞受体（TCR）Vβ基因库。在本研究中，我们测试了这种有限的Vβ基因库对移植排斥反应是否重要。从移植后2天浸润ACI心脏同种异体移植物的LEW淋巴细胞中建立了一个细胞系AL2-L3。该细胞系由CD4 + T细胞组成，这些T细胞主要识别供体移植物表达的II类RTI.B主要组织相容性复合体（MHC）分子。将该细胞系过继转移至亚致死剂量照射的LEW受体后，可引发供体心脏的急性排斥反应，中位生存时间（MST）为10.5天。与照射对照受体中同种异体移植物60天的MST相比，这种移植排斥率显著加快（P < 0.0007）。AL2-L3介导的移植排斥加速是供体特异性的，因为WF第三方心脏同种异体移植物的排斥出现延迟（MST = 28.5天）。该细胞系的Vβ基因库主要限于Vβ4、15和19基因的表达。对该细胞系β链cDNA的核苷酸序列分析表明，V基因库的有限使用与N、D和J区域无关。多种CDR3环和Jβ基因与选定的Vβ基因联合使用。这些数据为有限的Vβ基因库在该模型的心脏同种异体移植排斥反应中所起的作用提供了证据。同种异体移植物早期T细胞反应中Vβ基因库的有限使用可能为通过在器官移植时靶向选定的T细胞群体进行清除来治疗性破坏排斥反应提供机会。
