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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

发布时间:2018-08-20 11:21
【摘要】:目的检测CD4~+CD25~+Fox P3~+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、Fox P3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~+Fox P3~+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、Fox P3、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。
[Abstract]:Objective to detect the proportion of CD4 ~ CD25 ~ Fox P3- ~ regulatory T cell (Treg) in peripheral blood samples of children with acute B lymphocytic leukemia (pre-B ALL) and to explore the function of Helios gene in pre-B ALL peripheral blood Treg cells. Methods the peripheral blood samples of 10 patients with primary pre-B ALL in the ALL group and 6 children with osteoarthropathy were selected in the control group, and the peripheral blood samples of the children with tumor, blood system and immune system diseases were excluded. The percentage of Treg cells in pre-B ALL was detected by flow cytometry, and the expression of Helios Fox P3 and related transcription suppressor factor in ALL was detected by quantitative PCR technique. The expression of Helios in Treg cells was regulated by lentivirus transfection and siRNA technique, and the immunosuppressive function of Tregs was detected. Results the percentage of CD4 ~ CD25 ~ Fox P3~ cells in ALL group [(6.16 卤0.79)%] was significantly higher than that in control group [(2.62 卤0.34)%] (P0. 005). The up-regulated expression of Helios gene in Treg cells of ALL patients was positively correlated with the immunosuppressive function of Treg cells. Conclusion the abnormal immune function is correlated with the abnormal number of Treg cells in children with pre-BALL. The abnormal expression of Helios gene may affect the immunosuppressive function of Treg cells, and indirectly affect the immune regulation of leukemia children. Helios as a target gene may have therapeutic significance for immunotherapy with Treg cells.
【作者单位】: 山东大学深圳研究院;山东大学齐鲁医院儿科;
【基金】:深圳市科技研发基金知识创新计划(JCYJ2014 0418115449178) 山东省科技发展计划(2014GSF118131) 山东大学基本科研业务费(2014QLKY02&2014QY003-11)
【分类号】:R733.71


本文编号:2193396

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