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目的探讨CD134/CD134L共刺激分子对TH1/TH2细胞因子表达的影响及在狼疮性肾炎(LN)发病机制中的可能作用。方法活动期LN患者10例,分别采取外周静脉血,用密度梯度离心法制备新鲜PBMC,分成6组:(1)对照培养组;(2)单纯刺激组;(3)抗CD134组;(4)抗IL-4组;(5)rh-CD134∶Fc组;(6)地塞米松(Dex)组。另选取10例健康体检者作为健康对照组。采用ELISA法分别测定培养液上清中IFN-γ、IL-4、IL-10表达水平。结果(1)在抗CD3ε单抗PrIL-2刺激前,活动期LN患者PBMC培养液上清分泌的IFN-γ、IL-4和IL210水平都明显高于健康对照组;(2)在抗CD3ε单抗PrIL-2刺激下,活动期LN患者PBMC分泌的IFN2γ、IL-4和IL-10又较刺激前明显增加;(3)抗IL-4单抗、抗CD134单抗均可使经抗CD3ε单抗PrIL22刺激的LN患者PBMC分泌IL24、IL210水平显著下降,导致IFN2γ水平显著增高,免疫应答朝TH1方向偏离;(4)Dex能显著抑制抗CD3ε单抗PrIL22刺激的原代培养PBMC中IL24、IFN2γ的分泌水平,但对IL210的产生并没有明显的抑制或促进作用;(5)rhCD134∶Fc能显著降低抗CD3ε单抗PrIL-2刺激的原代培养PBMC中IFN-γ及IL-4、IL-10的分泌水平,对TH1和TH2细胞因子的产生都有显著抑制作用。结论糖皮质激素的抗炎机制具有多重性,对TH1、TH2细胞因子的作用并不均衡;抗CD134单抗对减轻LN患者PBMC的异常活化有一定作用;CD134-IgG融合蛋白与抗CD134单抗相比,抑制作用更明显,对急性期LN有更好的治疗作用。
Objective To investigate the effect of CD134 / CD134L costimulatory molecules on the expression of TH1 / TH2 cytokines and its possible role in the pathogenesis of lupus nephritis (LN). Methods Peripheral venous blood was collected from 10 patients with active LN and divided into 6 groups according to density gradient centrifugation: (1) control group, (2) stimulation group alone, (3) anti-CD134 group and ) Anti-IL-4 group, (5) rh-CD134: Fc group, and (6) dexamethasone group. Another 10 healthy people were selected as healthy control group. The levels of IFN-γ, IL-4 and IL-10 in the culture supernatant were determined by ELISA. Results (1) The levels of IFN-γ, IL-4 and IL210 secreted by PBMC culture supernatants of active LN patients before anti-CD3ε monoclonal antibody stimulation were significantly higher than that of healthy controls. (2) IL-4 and IL-10 secreted by peripheral blood mononuclear cells from patients with active LN increased significantly compared with those before stimulation. (3) Anti-IL-4 mAb and anti-CD134 mAb could induce anti-IL- The levels of IL24 and IL210 secreted by PBMC of CD3ε monoclonal antibody PrIL22-stimulated LN patients decreased significantly, leading to a significant increase of IFN2γ level and deviation of the immune response toward TH1. (4) Dex could significantly inhibit IL24 , But did not inhibit or promote the production of IL210. (5) rhCD134: Fc could significantly reduce the levels of IFN-γ and IL-4 in PBMC stimulated by anti-CD3ε monoclonal antibody PrIL-2 , IL-10 secretion level, have a significant inhibitory effect on TH1 and TH2 cytokine production. Conclusion The anti-inflammatory mechanism of glucocorticoid is multiplicative and its effect on TH1 and TH2 cytokines is not balanced. Anti-CD134 monoclonal antibody can reduce the abnormal activation of PBMC in LN patients. CD134-IgG fusion protein and anti-CD134 monoclonal antibody Compared with the more obvious inhibition, the acute phase of LN have a better therapeutic effect.