IL-21对HIV-1感染者外周血CD19+IgD+CD38hiB细胞及IL-10表达水平的影响  

Effects of IL-21 on the expression of Breg and IL-10 in HIV–infected individuals

作　　者：党便利 李建辉[1] 汪春付[1] 康文[1] 姚娜[1] 刘青[1] 王临旭[1] 孙永涛[1] 康文臻[1] DANG Bianli;LI Jianhui;WANG Chunfu;KANG Wen;YAO Na;LIU Qing;WANG Linxu;SUN Yongtao;KANG Wenzhen(Department of Infectious Disease,Tangdu Hospital,Fourth Military Medical University,Xi'an,710038,China)

机构地区：[1]第四军医大学唐都医院全军感染病诊疗中心,西安710038

出　　处：《中国艾滋病性病》2020年第4期346-350,共5页Chinese Journal of Aids & STD

基　　金：国家“十三五”科技重大专项(2017ZX10202101-003-007,2017ZX10202101-004-005,2017ZX10202203-008-003,2017ZX10202102-001-011);陕西省重点研发计划项目(S2018-YF-YBSF-0852)。

摘　　要：目的探讨白细胞介素-21(IL-21)/信号传导与转录激活因子3(STAT3)信号通路对1型艾滋病病毒(HIV-1)感染者外周血中调节B细胞(Breg)和IL-10表达水平的影响及与HIV-1感染疾病进展的关系。方法CD40L单独或联合IL-21刺激联合抗反转录病毒治疗(cART)前后的HIV感染者及健康对照者外周血单个核细胞(PBMC)20 min或120 h,用流式细胞术(FCM)检测CD19+IgD+CD38hiB细胞的比例变化,酶联免疫吸附试验(ELISA)测定培养上清中IL-21及IL-10水平,并用蛋白印迹试验(WB)结合FCM检测B细胞中STAT3的磷酸化水平。结果本次研究纳入的健康对照(HC)、未经治疗的HIV-1感染者及cART>48周的HIV-1感染者各15例。相对于健康对照组,HIV-1感染者CD4+T淋巴细胞数量显著降低(P<0.0001),cART后显著升高(P=0.0357);HIV-1感染者血浆中病毒载量为(5.025±0.9526)Lg10拷贝/mL,cART后其病毒载量被有效抑制;HIV-1感染者Breg的比例(P=0.0036)及IL-10水平(P=0.003)显著上调,且cART前后HIV-1感染者的IL-10水平与IL-21均呈正相关[(r=0.5823,P=0.0225),(r=0.5789,P=0.0237)];IL-21联合CD40L刺激能诱导HIV-1感染者STAT3磷酸化(P=0.0039),进而上调其CD19+IgD+CD38hiB细胞的比例(P=0.0348)及IL-10的表达水平(P=0.0153)。结论HIV-1感染导致CD19+IgD+CD38hiB细胞比例及IL-10表达水平均上调,且上调的IL-10水平与IL-21水平呈正相关。IL-21可能通过STAT3信号通路调控HIV-1感染者Breg细胞的分化及IL-10的分泌。Objective To study the effects of IL-21 on the differentiation of Breg in Chinese HIV-1 infected individuals during different disease states, and to investigate the differences for regulatory B cells(Breg, CD19^+IgD^+CD38hiB) reactivation to IL-21 stimulation. Methods The differentiation of Breg in peripheral blood and the expression of P-AKT and P-STAT3 in B cells stimulated by CD40L with or without IL-21 co-activation were determined by flow cytometry(FCM), the protein expression of P-STAT3 in B cells were detected by WB(Western Blot), and the levels of IL-10 and IL-21 in the supernatant were measured by ELISA in untreated groups, cART groups and healthy controls. Results Breg frequency(P = 0.0036), and IL-10 concentration(P = 0.003) were higher in untreated group than those in healthy controls, and the concentration of IL-10 was positive with IL-21 in untreated groups(r =0.5823,P =0.0225) and cART groups(r =0.5789,P =0.0237). IL-21 promoted the differentiation of Breg(P = 0.0348)and secretion of IL-10(P = 0.0153)via activation of STAT3 in the patients with HIV-1. Conclusion The ratio of Breg subsets and IL-10 Were increased due to HIV infection, and IL-21 can promote the differentiation of Breg and IL-10 secretion activation of STAT3.

关 键 词：艾滋病病毒 白细胞介素-21 信号传导与转录激活因子3 调节B细胞 

分 类 号：R512.91[医药卫生—内科学]