Arbour N, Rastikerdar E, McCrea E, Lapierre Y, Dörr J, Bar-Or A, Antel J P
Neuroimmunology Unit, Montreal Neurological Institute, McGill University, QC, Canada.
Mult Scler. 2005 Dec;11(6):652-7. doi: 10.1191/1352458505ms1222oa.
We measured the in vivo and in vitro effects of interferon (IFN)beta and glatiramer acetate (GA) on the expression of the regulatory molecule, tumor necrosis factor related apoptosis inducing ligand (TRAIL), in patients with multiple sclerosis (MS). We confirmed the prior observation that TRAIL is enhanced on anti-CD3 activated T cells by the in vitro addition of IFNbeta. T cells from IFNbeta-treated patients stimulated with anti-CD3 only, had higher levels of TRAIL than untreated patients, suggesting that in vivo IFNbeta exposure has an effect on TRAIL expression in association with T cell activation. In vitro IFNbeta-induced TRAIL upregulation on anti-CD3 or phytohemagglutinin-activated T cells was comparable for IFNbeta-treated and non-treated MS patients and controls, indicating that IFN receptors were neither saturated nor down-regulated by current IFNbeta therapy. Although GA in vivo or in vitro did not induce TRAIL, the IFNbeta +GA combination in vitro enhanced TRAIL expression to higher levels than IFNbeta alone on CD4+ T cells obtained from MS patients, regardless of GA treatment status, and healthy donors, and on GA reactive T cell lines derived from GA-treated patients or controls. Whether any observed therapeutic effects of GA/IFNbeta combination therapy will correlate with TRAIL expression and function remains to be determined.
我们测量了干扰素（IFN）β和醋酸格拉替雷（GA）对多发性硬化症（MS）患者调节分子肿瘤坏死因子相关凋亡诱导配体（TRAIL）表达的体内和体外作用。我们证实了之前的观察结果，即体外添加IFNβ可增强抗CD3激活的T细胞上的TRAIL表达。仅用抗CD3刺激的IFNβ治疗患者的T细胞，其TRAIL水平高于未治疗患者，这表明体内IFNβ暴露与T细胞激活相关，对TRAIL表达有影响。对于IFNβ治疗和未治疗的MS患者及对照组，体外IFNβ诱导抗CD3或植物血凝素激活的T细胞上TRAIL上调的情况相当，这表明当前的IFNβ治疗既未使IFN受体饱和，也未使其下调。尽管GA在体内或体外均未诱导TRAIL，但体外IFNβ与GA联合使用时，无论GA治疗状态如何，在来自MS患者和健康供体的CD4 + T细胞以及来自GA治疗患者或对照组的GA反应性T细胞系上，均可将TRAIL表达增强至高于单独使用IFNβ的水平。GA/IFNβ联合治疗所观察到的任何治疗效果是否与TRAIL表达和功能相关，仍有待确定。
