IL-27调控未经抗病毒治疗的HIV-1感染者CD8^+T淋巴细胞功能耗竭的研究  

IL-27 contributes to naive HIV-1 carriers’ CD8^+ T cells exhaustion

作　　者：魏乾奇 庄严[1] 孙永涛[1] WEI Qianqi;ZHUANG Yan;SUN Yongtao(Department of Infectious Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi＇ an 710038, Shaanyi, China)

机构地区：[1]第四军医大学唐都医院传染科

出　　处：《中国艾滋病性病》2018年第5期432-435,共4页Chinese Journal of Aids & STD

基　　金：国家“十三五”科技重大专项(2017ZX10202102-002-001)~~

摘　　要：目的探究未经抗病毒治疗的艾滋病病毒1型（HIV-1）感染者CD8＋T淋巴细胞（简称CD8细胞）在白细胞介素27（IL-27）刺激下,表面受体及核内因子的变化情况,进一步理解IL-27在HIV-1感染中发挥的作用。方法分离得到22例符合条件的HIV-1感染者CD8细胞,经CD3＋ CD28＋抗体刺激后,加或不加人重组IL-27蛋白,体外培养48小时后,通过实时荧光定量反转录聚合酶链反应（real-time RT-PCR）检测WSX-1、Tbet,流式细胞学方法检测CTLA-4、PD-1、Tim-3的变化。结果 HIV-1感染者CD8细胞在体外培养2天后,与无IL-27培养组相比,IL-27刺激组CD8细胞WSX-1受体信使核糖核酸（mRNA）水平表达降低。同时在IL-27刺激组中,表达抑制性受体CTLA-4、PD-1、Tim-3的CD8细胞比例均明显增高,转录因子Tbet的mRNA表达量上升。结论 IL-27在HIV-1慢性感染中,会受自身的分泌影响而在CD8细胞中下调WSX-1的表达,存在着一定的负反馈机制。同时IL-27使CD8细胞表达与功能耗竭,相关的抑制性受体的细胞比例增多,参与调控CD8细胞功能耗竭。Objective To investigate the expression of WSX-1,CTLA-4,PD-1,Tim-3 and transcription factor Tbet in naive HIV-1 carriers’ CD8＋T cells cultured with IL-27 stimulation to clarify the function of IL-27 during HIV-1 infection.Methods We recruited 22 HIV-1 carriers whose selected CD8~＋T cells were cultured with or without human recombination IL-27 protein after CD3~＋CD28~＋antibody stimulation for 48 hours,then cells were detected by the expression of WSX-1,Tbet mRNA,and analyzed in frequencies of CTLA-4＋,PD-1＋,Tim-3＋.Results Selected 22 HIV-1 carriers’ CD8~＋T cells were cultured in vitro for 2 days.IL-27 treatment could reduce the expression of WSX-1 mRNA.In the meantime,CTLA-4,PD-1 and Tim-3 expression on CD8~＋T cells increased as well as Tbet transcription up-regulated.Conclusion During HIV-1 chronic infection,IL-27 is influenced by its own secretion,involved in a feedback loop characteristic by down-regulation of WSX-1 in CD8~＋T cells.We presume that IL-27 functions in regulating CD8~＋T-cell exhaustion is characteristic by expressing higher levels of inhibitory receptors.Furthermore,IL-27 induces a series of downstream signal changes including important transcription factor Tbet,balancing immune response in viral chronic infection.

关 键 词：1型艾滋病病毒 细胞因子 CD8+T淋巴细胞 功能耗竭 转录因子 

分 类 号：R512.91[医药卫生—内科学]