Numbers of Foxp3-expressing CD4+CD25high T cells do not correlate with the establishment of long-term tolerance after allogeneic stem cell transplantation
Numbers of Foxp3-expressing CD4+CD25high T cells do not correlate with the establishment of long-term tolerance after allogeneic stem cell transplantation
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DOI：
10.1016/j.exphem.2005.05.001
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发表时间：
2005-08-01
影响因子：
2.6
通讯作者：
Socié, G
中科院分区：
文献类型：
--
作者：
Meignin, W;de Latour, RP;Socié, G
Objective.表达高水平CD 25的调节性CD 4 T细胞在维持对自身抗原的耐受性中起着至关重要的作用，并且是诱导对同种异体抗原的无应答性所必需的。异基因干细胞移植后长期CD 4（+）CD 25（高）T细胞重建尚不清楚。在这里，我们评估了该T细胞亚群的恢复是否可能与完全供体/受体耐受性的建立有关。在31例患者中，通过荧光激活细胞分选仪（FACS）分析确定了CD 4（+）CD 25（高）T细胞的频率，平均随访时间超过31个月。采用实时荧光定量聚合酶链反应（RT-PCR）检测Foxp 3 mRNA的表达水平。有或没有移植物抗宿主病（GvHD）的患者有显着的和持续的CD 4 T细胞淋巴细胞减少症。所有患者和健康对照组中CD 25（高）细胞的相对频率和FoxP 3 mRNA的表达水平相似。Foxp 3表达的CD 4（+）CD 25 high T细胞数量在GvHD患者和非GvHD患者中无显著差异。最后，年龄较小和既往无GvHD与CD 4（+）CD 25（高）T细胞恢复显著相关。移植患者中Foxp 3表达的CD 4（+）CD 25（高）T细胞数量较少不是该区室的特定默认值，而是异基因干细胞移植后整体CD 4 T细胞淋巴细胞减少症的结果。此外，CD 25（+）T细胞区室中Foxp 3 mRNA的水平不能预测GvHD的长期发展。(c)2005年国际实验血液学学会。由爱思唯尔公司出版
Objective. Regulatory CD4 T cells that express high levels of CD25 play a vital role in the maintenance of tolerance to self antigens and are required for the induction of nonresponsiveness to alloantigens. The long-term CD4(+)CD25(high) T-cell reconstitution after allogeneic stem cell transplantation is unknown. Here, we evaluated whether recovery of this T-cell subset might be linked to the establishment of full donor/recipient tolerance.Methods. The frequency of CD4(+)CD25(high) T cells was determined by Fluorescence Activated Cell Sorter (FACS) analysis in 31 patients, with a mean follow-up of more than 31 months posttransplant. The expression levels of Foxp3 mRNA were assessed by quantitative real-time polymerase chain reaction (RT-PCR).Results. Patients with or without graft-versus-host disease, (GvHD) had significant and persistent CD4 T-cell lymphopenia. The relative frequency of CD25(high) cells and the expression levels of FoxP3 mRNA within this subset were similar between all patients and healthy controls. No significant difference was found in the number of Foxp3-expressing CD4(+)CD25high T cells in patients with or without GvHD. Finally, younger age and absence of previous GvHD were significantly linked to CD4(+)CD25(high) T-cell recovery.Conclusion. The low number of Foxp3-expressing CD4(+)CD25(high) T cells in grafted patients is not a specific default of this compartment but a consequence of global CD4 T-cell lymphopenia after allogeneic stem cell transplantation. Moreover, levels of Foxp3 mRNA in the CD25(+) T-cell compartment do not allow predicting the development of GvHD in the long term. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc.