初发1型糖尿病患者外周血滤泡辅助性T细胞的变化特点
Changes of follicular helper T cells in peripheral blood of patients with newly-diagnosed type 1 diabetes mellitus
目的 观察初发1型糖尿病患者外周血单个核细胞(peripheral blood mononuclear cell,PBMC)扣滤泡辅助性T细胞(follicular helperT cells,Tfh)的数目和功能的变化,并与B淋巴细胞的变化及自身抗本等临床资料进行相关性分析,探讨Tfh参与1型糖尿病发病的免疫学机制.方法 收集18例新诊断的1型糖尿病患者和15名健康对照者外周血全血,分离PBMC后流式细胞仪检测CD4+CXCR5+ ICOS+ Tfh及CD19+B淋巴细胞比例,观察二者在1型糖尿病患者中的变化趋势;实时荧光定量PCR检测Tfh细胞因子白细胞介素21(IL-21)及人B细胞淋巴瘤因子6(Bcl-6)的mRNA水平;分析Tfh细胞与抗谷氨酸脱羧酶抗本(GADA)滴度的相关性.结果 (1)与正常对照组相比,新诊断的1型糖尿病患者外周血中的Tfh细胞比例显著上升[(0.09±0.01对0.20±0.01)%,P<0.01],同时伴有B淋巴细胞比例增多[(1.68±0.16对3.40±0.25)%,P<0.01];(2)在1型糖尿病患者PBMC中Bcl-6的mRNA表达下调30% (P<0.01),IL-21的mRNA水平下降35%(P<0.05);(3)1型糖尿病患者PBMC中Tfh水平与GADA水平呈显著正相关(r=0.792,P<0.01).结论 初发1型糖尿病患者外周血Tfh比例显著增加,伴随B淋巴细胞及GADA滴度的上升,表明Tfh可能参与了1型糖尿病的发病.
更多Objective To observe the changes in follicular helper T cells (Tfh) in peripheral blood mononuclear cell (PBMC) of newly-diagnosed patients with type 1 diabetes mellitus (T1DM),to analyze its relationship with B lymphocyte and autoantibodies,and to explore the role played by Tfh cells in the pathogenesis of T1DM.Methods Eighteen patients with newly-diagnosed T1DM and 15 healthy control subjects were enrolled.The percentages of Tfh cells and B cells in PBMC with respective CD4+CXCRS+ICOS+and CD19+markers were assessed by flowcytometry.The mRNA expressions of interluekin 21 (IL-21) and Bcl-6 were detected in two groups by realtime PCR,and the association between Tfh and glutamic acid decarboxylase antibody (GADA) was analyzed.Results (1) The proportions of Tfh [(0.09 ± 0.01 vs 0.20 ± 0.01) %,P<0.01] and B lymphocyte [(1.68 ± 0.16 vs 3.4 ±0.25)%,P<0.01] in PBMC from T1DM group were significantly higher than those in control group.(2) In comparison with control group,mRNA levels of Bcl-6 and IL-21 in PBMC of T1DM group were decreased by 30% (P<0.01) and 35% (P<0.05).(3) A positive correlation between the amount of Tfh cell and the titer of GADA was found (r =0.792,P < 0.01).Conclusion The close relationship of Tfh cells with clinical and biochemical characteristics in newly-diagnosed patients with T1DM demonstrates an important role which may be played by Tfh cells in the pathogenesis of T1DM.
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