人树突状细胞的成熟状态体外对Glatiramer acetate特异的T细胞系的调控作用(英文)

Modulation Effects of Human Immature and Mature Dendritic Cells on Glatiramer Acetate Specific T Cell Lines In Vitro

为了了解树突状细胞 (DC)成熟状态对Glatirameracetate(GA)特异的T细胞分化的影响 ,在体外条件下 ,分析了从多发性硬化症 (MS)病人外周血单个核细胞诱导的成熟与未成熟的树突状细胞对来自多发性硬化症病人的GA特异的T细胞系增殖及细胞因子产生的影响。结果显示 ,体外条件下 ,从MS病人外周血的单个核细胞易于诱导GA抗原特异的T细胞系 (TCL) ;5 μg/ml的脂多糖 (LPS)在 2 4小时内可有效诱导DC的成熟。同未成熟的DC相比 ,成熟的DC更能有效地刺激GA抗原特异的TCL的增殖 ;GA抗原特异的TCL产生高水平的IL 2 ,IL 4 ,IFN γ ,IL 10及低水平的IL 6 ;成熟DC能促进GA抗原特异的TCL的IL 6和IL 10的分泌 ,但下调IL 2 ,IL 4及IFN γ的产生。结论 :DC的成熟状态调控TCL的增殖及细胞因子的产生。

A large body of evidence demonstrates that dendritic cells (DC) play a pivotal role in the control of immunity by priming and tolerizing T cells. In multiple sclerosis (MS), autoreactive T cells are proposed to play a pathogenic role by secreting pro inflammatory cytokines, but comparison studies on the effects of immature and mature dendritic cells on the cytokines profile of antigen specific T cell lines are lacking. To evaluate the actions of dendritic cell maturation on T cell polarization, the effects of immature and mature dendritic cells derived from MS patients on in vitro proliferative responses, and cytokine production by glatiramer acetate (GA) specific T cell lines (TCL) derived from MS patients were analyzed. The results demonstrated that it is easy to derive GA specific TCL from MS patients with high specificity; lipopolysaccharide can efficiently induce DC maturation within 24 hours at a concentration of 5 μg/ml; mature DC showed higher co stimulatory capacity of GA specific TCLs than immature DC. GA specific TCLs produce dominantly IL 2, IL 4, IFN γ and IL 10, but low levels of IL 6. In contrast to immature DC, mature DC enhanced capacity to induce IL 6 and IL 10 secretion, but down regulate IL 2, IL 4 and IFN γ production by GA specific TCLs. It is concluded that DC maturation status modulating proliferation of TCL and production of cytokines may represent another focus for the study on both immuno pathogenesis and immunotherapeutic interventions in MS.