Key Laboratory for Experimental Teratology of the Ministry of Education and Institute of Experimental Nuclear Medicine, School of Medicine, Shandong University, Jinan, Shandong, PR China.
Cell Transplant. 2011;20(2):333-50. doi: 10.3727/096368910X552844. Epub 2011 Feb 3.
Allograft rejection is a leading cause for the failure of allotransplantation. CD4(+) T cells play critical roles in this process. The identification of genes that alternatively expressed in CD4(+) T cells during allograft rejection will provide critical information for studying the mechanism of allograft rejection, finding specific gene markers for monitoring, predicting allograft rejection, and opening new ways to regulate and prevent allograft rejection. Here, we established allograft and isograft transplantation models by adoptively transferring wild-type BALB/c mouse CD4(+) T cells into severe combined immunodeficient (SCID) mice with a C57BL/6 or BALB/c mouse skin graft. Using the whole transcriptome sequencing-based serial analysis of gene expression (SAGE) technology, we identified 97 increasingly and 88 decreasingly expressed genes that may play important roles in allograft rejection and tolerance. Functional classification of these genes shows that apoptosis, transcription regulation, cell growth and maintenance, and signal transduction are among the frequently changed functional groups. This study provides a genome-wide view for the candidate genes of CD4(+) T cells related to allotransplantation, and this report is a good resource for further microarray studies and for identifying the specific markers that are associated with clinical organ transplantations.
同种异体移植物排斥反应是导致同种异体移植失败的主要原因。CD4(+) T 细胞在这一过程中起着关键作用。鉴定在同种异体排斥反应过程中 CD4(+) T 细胞中差异表达的基因，将为研究同种异体排斥反应的机制、寻找监测、预测同种异体排斥反应的特异性基因标记以及为调节和预防同种异体排斥反应开辟新途径提供重要信息。在这里，我们通过将野生型 BALB/c 小鼠 CD4(+) T 细胞过继转移到具有 C57BL/6 或 BALB/c 小鼠皮肤移植物的严重联合免疫缺陷 (SCID) 小鼠中，建立了同种异体和同种移植模型。使用基于全转录组测序的基因表达序列分析 (SAGE) 技术，我们鉴定了 97 个表达上调和 88 个表达下调的基因，这些基因可能在同种异体排斥反应和耐受中发挥重要作用。这些基因的功能分类表明，凋亡、转录调控、细胞生长和维持以及信号转导是经常变化的功能组之一。本研究为 CD4(+) T 细胞与同种异体移植相关的候选基因提供了一个全基因组视角，本报告为进一步的微阵列研究和鉴定与临床器官移植相关的特异性标记物提供了很好的资源。
