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  

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

作　　者：张榕[1] 王晓非[1] 赵丽娟[1] 肖卫国[1] 姜奕[2] 

机构地区：[1]中国医科大学附属第一医院风湿免疫科,沈阳110001 [2]中国医科大学附属第一医院中心实验室,沈阳110001

出　　处：《中华风湿病学杂志》2008年第4期222-225,共4页Chinese Journal of Rheumatology

基　　金：国家自然科学基金资助项目（30571701）;辽宁省教育厅青年基金资助项目（05L538）

摘　　要：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（MTr）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制（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〈0．01），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-1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SLET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。Objective To investigate the effect of T lymphocyte proliferation,Thl 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 IFN-γ and IL-4 in supernatants were measured by ELISA. Results ① The proliferation of T cells from SLE patients stimulated with anti-CD3 McAb were significantly higher than those of T cells without stimulation（P〈 0.01 ）. But the proliferation of T cells from SLE patients were inhibited by anti-4-1BB McAb. ② The levels of IFN-γ and IL-4 in SLE were significantly higher than those of normal controls （P〈0.01）. There were more expression 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〈0.05）, and especially the level of IL-4 was markedly decreased. Conclusion Blocking 4-1BB/4-1BBL can significantly inhibit the abnormal activation of T cells and the secretion of Thl and Th2 cytokines of SLE.

关 键 词：红斑狼疮 系统性 4-1BB 抗4-IBB单抗 干扰素Ⅱ型 白细胞介素4 

分 类 号：R686[医药卫生—骨科学]