Kollins D, Stoelcker B, Hoffmann U, Bergler T, Reinhold S, Banas M C, Rümmele P, Farkas S, Krämer B K, Banas B
Department of Internal Medicine II, Institute of Pathology, School of Medicine, University Hospital Regensburg, Regensburg, Germany.
Clin Nephrol. 2011 Feb;75(2):91-100.
The interpretation of a cellular infiltrate as cytotoxic or tolerogen represents an unsolved challenge in current transplantation. The so-called regulatory CD4+ CD25+ T-cells which express the FOXP3 gene have received increasing interest with respect to this question. The existing studies concerning the role of FOXP3+ Tregs for transplant tolerance yielded contradictory results.
We examined the numbers of the FOXP3+ Tregs in two groups of renal allograft biopsies both showing cellular infiltration, but either without (n=29) or with signs of acute cellular rejection (n=26), by means of immunofluorescence and correlated the amount of FOXP3+ Tregs to renal function at the time of biopsy and after 1 and 2 years of follow up.
The number of FOXP3+ Tregs within infiltrates in non-rejecting biopsies did not correlate with renal function after 1 and 2 years. There were no significant differences in the numbers of FOXP3+ Tregs between biopsies with or without borderline infiltrates. Increased numbers of FOXP3+ Tregs were not associated with an ameliorated severity of graft rejection and did not correlate with outcome after the rejection episode and renal function after 1 and 2 years.
The identification of the FOXP3+ regulatory cells within the allograft cannot be considered as an appropriate marker for the interpretation of infiltrates as cytotoxic or tolerogenic or as a prognostic marker for later transplant function.
在当前移植领域,将细胞浸润解释为具有细胞毒性还是具有免疫耐受原性是一个尚未解决的难题。就这个问题而言,表达叉头框蛋白3(FOXP3)基因的所谓调节性CD4 + CD25 + T细胞受到了越来越多的关注。现有的关于FOXP3 +调节性T细胞(Tregs)在移植耐受中作用的研究得出了相互矛盾的结果。
我们通过免疫荧光检查了两组肾移植活检组织中FOXP3 + Tregs的数量,这两组活检组织均显示有细胞浸润,但一组无急性细胞排斥迹象(n = 29),另一组有急性细胞排斥迹象(n = 26),并将FOXP3 + Tregs的数量与活检时、随访1年和2年后的肾功能进行关联分析。
在无排斥反应的活检组织浸润中,FOXP3 + Tregs的数量与1年和2年后的肾功能无关。有或无临界浸润的活检组织中FOXP3 + Tregs的数量没有显著差异。FOXP3 + Tregs数量增加与移植排斥反应严重程度的改善无关,也与排斥反应发作后的结局以及1年和2年后的肾功能无关。
不能将同种异体移植中FOXP3 +调节性细胞的鉴定视为将浸润解释为具有细胞毒性或免疫耐受原性的合适标志物,也不能将其视为移植后期功能的预后标志物。