INSERM Unité 643, CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, Université de Nantes, Faculté de Médecine de Nantes. RTRS Centaure, Nantes, France.
Eur J Immunol. 2010 Nov;40(11):3280-90. doi: 10.1002/eji.201040301. Epub 2010 Oct 27.
The long-term stability of renal grafts depends on the absence of chronic rejection. As T cells play a key role in rejection processes, analyzing the T-cell repertoire may be useful for understanding graft function outcomes. We have therefore investigated the power of a new statistical tool, used to analyze the peripheral blood TCR repertoire, for determining immunological differences in a group of 229 stable renal transplant patients undergoing immunosuppression. Despite selecting the patients according to stringent criteria, the patients displayed heterogeneous T-cell repertoire usage, ranging from unbiased to highly selected TCR repertoires; a skewed TCR repertoire correlating with an increase in the CD8(+) /CD4(+) T-cell ratio. T-cell repertoire patterns were compared in patients with clinically opposing outcomes i.e. stable drug-free operationally tolerant recipients and patients with the "suspicious" form of humoral chronic rejection and were found significantly different, from polyclonal to highly selected TCR repertoires, respectively. Moreover, a selected TCR repertoire was found to positively correlate with the Banff score grade. Collectively, these data suggest that TCR repertoire categorization might be included in the calculation of a composite score for the follow-up of patients after kidney transplantation.
肾移植的长期稳定性取决于是否存在慢性排斥反应。由于 T 细胞在排斥过程中起关键作用,因此分析 T 细胞受体库可能有助于了解移植物功能的结果。因此,我们研究了一种新的统计工具的能力,该工具用于分析外周血 TCR 库,以确定 229 名接受免疫抑制治疗的稳定肾移植患者组中的免疫差异。尽管根据严格的标准选择了患者,但患者表现出不同的 T 细胞受体库使用情况,从无偏倚到高度选择的 TCR 库;TCR 库的偏斜与 CD8(+) / CD4(+) T 细胞比值的增加相关。比较了具有临床相反结果的患者(即稳定的、无需药物治疗的、具有操作性免疫耐受性的受者,以及具有“可疑”形式的体液性慢性排斥反应的患者)的 T 细胞受体库模式,发现它们从多克隆到高度选择的 TCR 库分别有显著差异。此外,发现选择的 TCR 库与 Banff 评分等级呈正相关。总的来说,这些数据表明 TCR 受体库分类可能包含在计算肾移植后患者随访的综合评分中。