Helios在儿童急性淋巴细胞性白血病调节性T细胞中的表达及功能

doi:10.6040/j.issn.1671-7554.0.2016.782

摘要/Abstract

摘要： 目的检测CD4⁺CD25⁺FoxP3⁺调节性T细胞(Treg)在儿童急性B淋巴细胞白血病(pre-B ALL)外周血样本中的比例,探讨Helios基因在pre-B ALL外周血Treg细胞中的功能。方法 ALL组选取10例初发pre-B ALL外周血标本,对照组选取6例行骨关节病手术并排除肿瘤、血液系统、免疫系统疾病的患儿外周血标本;采用流式细胞术检测Treg细胞在pre-B ALL 中CD4⁺细胞的比例,通过定量PCR技术检测Helios、FoxP3及相关转录抑制因子在ALL中CD4⁺CD25⁺Treg细胞中的表达;通过慢病毒转染和siRNA技术在Treg细胞中调节Helios表达,检测Tregs免疫抑制功能的变化。结果 ALL组中CD4⁺CD25⁺FoxP3⁺细胞占CD4⁺T细胞比例［(6.16±0.79)%］显著高于对照组［(2.62±0.34)%］(P=0.005);Helios、FoxP3、TGF-β1 mRNA在ALL患者Treg细胞中上调表达;Helios基因的异常表达与Treg细胞的免疫抑制功能呈正相关。结论儿童pre-BALL发病过程中,免疫功能异常与Treg细胞数量异常相关。其中Helios基因的异常表达可通过影响Treg细胞的免疫抑制功能,间接影响白血病患儿的免疫调控。Helios作为靶基因可能对以Treg细胞为主的免疫治疗具有治疗意义。

关键词: 急性淋巴细胞白血病, 调节性T细胞, Helios基因, 转化生长因子-β1

Abstract: Objective To detect the proportion of human CD4⁺CD25⁺FoxP3⁺ regulatory T cells(Treg)in patients with pre-B acute lymphoblastic leukemia(ALL)and to explore the role of transcriptional factor Helios in pre-B ALL Treg cells. Methods A total of 10 primary ALL cases(ALL group)and 6 cases of osteoarthropathy free from tumors, hematological diseases and immunological diseases(control group)were involved. Peripheral blood samples were collected from all cases. The proportion of Treg cells was tested with flow cytometry, and the expressions of Helios, FoxP3 and related transcription inhibitors in CD4⁺CD25⁺ Treg cells of pre-B ALL samples were tested with real-time quantitative polymerase chain reaction(qRT-PCR). The lentiviral vectors expressing Helios mRNA and Helios-siRNA were constructed to regulate Helios expression in vitro to assay the role of Helios. Results The percentage of Treg cells in the ALL group and control group was(6.16±0.79)% and(2.62±0.34)%, respectively, with significant statistical difference(P=0.005). The expressions of Helios, FoxP3 and in TGF-β1 mRNA were upregulated in Treg cells. The abnormal expression of Helios was positively correlated to the immunosupression function of Treg cells. 山东大学学报 (医学版)55卷4期 -李雪,等.Helios在儿童急性淋巴细胞性白血病调节性T细胞中的表达及功能 \=- Conclusion The immunosuppressive function of Treg cells can affect the immunity of pediatric pre-B ALL by regulating the expression of Helios gene. Helios gene plays an important role in the function of ALL Treg cells. Helios may serve as a target gene in the immunotherapy of Treg-dependent cancer.

Key words: Helios gene, TGF-β1, Acute lymphoblastic leukemia, Regulatory T cells

中图分类号:

R725.5

李雪,李栋,时庆,周盼盼,鞠秀丽. Helios在儿童急性淋巴细胞性白血病调节性T细胞中的表达及功能[J]. 山东大学学报（医学版）, 2017, 55(4): 76-81.

LI Xue, LI Dong, SHI Qing, ZHOU Panpan, JU Xiuli. Expression and role of Helios gene in regulatory T cells of pediatric precursor B-cell acute lymphoblastic leukemia[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(4): 76-81.

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