【摘要】：目的檢測(cè)CD4~+CD25~+Fox P3~+調(diào)節(jié)性T細(xì)胞(Treg)在兒童急性B淋巴細(xì)胞白血病(pre-B ALL)外周血樣本中的比例,探討Helios基因在pre-B ALL外周血Treg細(xì)胞中的功能。方法 ALL組選取10例初發(fā)pre-B ALL外周血標(biāo)本,對(duì)照組選取6例行骨關(guān)節(jié)病手術(shù)并排除腫瘤、血液系統(tǒng)、免疫系統(tǒng)疾病的患兒外周血標(biāo)本;采用流式細(xì)胞術(shù)檢測(cè)Treg細(xì)胞在pre-B ALL中CD4~+細(xì)胞的比例,通過(guò)定量PCR技術(shù)檢測(cè)Helios、Fox P3及相關(guān)轉(zhuǎn)錄抑制因子在ALL中CD4~+CD25~+Treg細(xì)胞中的表達(dá);通過(guò)慢病毒轉(zhuǎn)染和siRNA技術(shù)在Treg細(xì)胞中調(diào)節(jié)Helios表達(dá),檢測(cè)Tregs免疫抑制功能的變化。結(jié)果 ALL組中CD4~+CD25~+Fox P3~+細(xì)胞占CD4~+T細(xì)胞比例[(6.16±0.79)%]顯著高于對(duì)照組[(2.62±0.34)%](P=0.005);Helios、Fox P3、TGF-β1 mRNA在ALL患者Treg細(xì)胞中上調(diào)表達(dá);Helios基因的異常表達(dá)與Treg細(xì)胞的免疫抑制功能呈正相關(guān)。結(jié)論兒童pre-BALL發(fā)病過(guò)程中,免疫功能異常與Treg細(xì)胞數(shù)量異常相關(guān)。其中Helios基因的異常表達(dá)可通過(guò)影響Treg細(xì)胞的免疫抑制功能,間接影響白血病患兒的免疫調(diào)控。Helios作為靶基因可能對(duì)以Treg細(xì)胞為主的免疫治療具有治療意義。
[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 鹵0.79)%] was significantly higher than that in control group [(2.62 鹵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.
【作者單位】： 山東大學(xué)深圳研究院;山東大學(xué)齊魯醫(yī)院兒科;
【基金】：深圳市科技研發(fā)基金知識(shí)創(chuàng)新計(jì)劃(JCYJ2014 0418115449178) 山東省科技發(fā)展計(jì)劃(2014GSF118131) 山東大學(xué)基本科研業(yè)務(wù)費(fèi)(2014QLKY02&2014QY003-11)
【分類(lèi)號(hào)】：R733.71
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本文編號(hào)：2193396