阻断4-1BB/4-1BBL通路对系统性红斑狼疮T淋巴细胞增殖和细胞因子分泌的影响

目的 研究共刺激分子4-1BB/4-1BBL对系统性红斑狼疮(SLE)T淋巴细胞增殖与Th1/Th2细胞因子分泌的影响,探讨其在SLE发病机制中的作用.方法 采用四甲基噻唑蓝(MTT)法和酶联免疫吸附试验(ELISA)法检测体外培养的30例SLE患者外周血T淋巴细胞应用抗4-1BB单抗阻断前后T淋巴细胞增殖及干扰素(IFN)-γ和白细胞介素(IL)-4分泌水平,以20名健康志愿者为正常对照.结果 ①SLE患者T淋巴细胞经抗CD3单抗刺激后增殖明显大于活化前(P＜0.01),而应用抗4-1BB单抗阻断后T淋巴细胞的增殖明显受抑N(p＜0.01 .②SLE患者T淋巴细胞培养上清中IFN-γ和IL-4水平明显高于正常对照组(P＜O.01),而且经抗CD3单抗刺激活化后,SLE患者T淋巴细胞分泌的IFN-γ和IL-4水平显著高于活化前(P＜0.01),但是应用抗4-1BB单抗阻断后培养上清中IFN-γ和IL-4水平明显下降(P＜0.05,),以IL-4水平的减少最为显著.结论 抗4-1BB单抗可显著抑制SLE T淋巴细胞的异常活化及Th1和Th2细胞因子的分泌,减轻SLE的免疫损伤.

Effect of blocking 4-1BB/4-1BBL on the proliferation of T cell and the expression of Th1 and Th2 cytokines in T cells from patients with systemic lupus erythematosus

Objective To investigate the effect of T lymphocyte proliferation,Th1 and Th2 cytokines on T cells from systemic lupus erythematosus (SLE)patients by blocking 4-1BB/4-1BBL.Methods The proliferation of T cells from 30 SLE patients and 20 normal controls was detected by MTT and the levels of patients stimulated with anti-CD3 McAb were significantly higher than those of T cells without stimulation(P＜IFN-γand IL-4 in SLE were significantly higher than those of normal controls(P＜0.01).There were more ex-pression of IFN-γ and IL-4 in supernatant of T cells from SLE after stimulated with anti-CD3 McAb(P＜0.01).However,the production of IFN-γ and IL-4 was inhibited by anti-4-1BB McAb(P＜O.05),and especially the level of IL-4 was markedly decreased.Conclusion Blocking 4-1BB/4-IBBL can significantlv inhibit the abnormal activation of T cells and the secretion of Thl and Th2 cytokines of SLE.