Ponciano Viviane C, Renesto Paulo G, Nogueira Eliana, Rangel Erika B, Cenedeze Marcos A, Franco Marcello F, Câmara Niels O S, Pacheco-Silva Alvaro
Laboratory of Clinical and Experimental Immunology, Nephrology Division, Universidade Federal de São Paulo, Rua Botucatu 740, Vila Clementino, 04023-900, São Paulo, SP, Brazil.
Transpl Immunol. 2007 Apr;17(3):215-22. doi: 10.1016/j.trim.2006.11.003. Epub 2006 Dec 6.
Tim-3 was recently described as a Th1-specific molecule, participating in the regulation of immune responses and in the induction of allograft tolerance. Here, we studied Tim-3 mRNA expression together with molecular markers of T-cell activation and cytotoxicity, in rejected human kidney grafts.
Twenty human kidney grafts that had undergone nephrectomy due to an irreversible acute rejection episode were studied. We quantified intragraft expression of Tim-3, granzyme B, perforin, IFN-gamma and Fas-ligand mRNA by real-time RT-PCR, with probes and primers TaqMan. Protocol biopsies were studied as controls. Statistical analyses were performed to compare groups, and to investigate the potential association with gene transcripts measures and rejection.
All molecules studied were up-regulated in the rejection group compared with controls (p<0.001). Acute rejection type III (Banff 97) profiles were associated with higher values, where granzyme B and perforin presented the highest (5672.51+/-9002.16 and 1866.59+/-2426.38, respectively) and Tim-3 had the lowest ones (166.62+/-174.94). Tim-3 had also a lower expression in those patients that did not respond to anti-rejection therapy. There was a positive correlation between Tim-3 and IFN-gamma mRNA expression levels (r(2)=0.73; p<0.001).
Our results corroborate the concept that acute rejection is an active process, where inflammatory as well as regulatory factors have their roles. Severe episodes of acute rejection were associated with higher expression of cytotoxic molecules and lower expression of potential regulatory molecule.
Tim-3最近被描述为一种Th1特异性分子，参与免疫反应的调节以及同种异体移植耐受的诱导。在此，我们研究了Tim-3 mRNA在人肾移植排斥反应中的表达，并与T细胞活化和细胞毒性的分子标志物进行了对比。
对20例因不可逆性急性排斥反应而接受肾切除术的人肾移植进行研究。我们使用TaqMan探针和引物，通过实时逆转录聚合酶链反应（RT-PCR）定量检测移植肾内Tim-3、颗粒酶B、穿孔素、干扰素-γ（IFN-γ）和Fas配体mRNA的表达。将方案活检组织作为对照。进行统计分析以比较各组，并研究基因转录物测量值与排斥反应之间的潜在关联。
与对照组相比，排斥反应组中所有研究的分子均上调（p<0.001）。III型急性排斥反应（Banff 97）特征与更高的值相关，其中颗粒酶B和穿孔素的值最高（分别为5672.51±9002.16和1866.59±2426.38），而Tim-3的值最低（166.62±174.94）。在那些对抗排斥治疗无反应的患者中，Tim-3的表达也较低。Tim-3与IFN-γ mRNA表达水平之间存在正相关（r²=0.73；p<0.001）。
我们的结果证实了急性排斥反应是一个活跃过程的概念，其中炎症因子和调节因子都发挥了作用。严重的急性排斥反应发作与细胞毒性分子的高表达和潜在调节分子的低表达相关。
