Correale Jorge, Farez Mauricio
Department of Neurology, Raúl Carrea Institute for Neurological Research (FLENI), Buenos Aires, Argentina.
Ann Neurol. 2007 Feb;61(2):97-108. doi: 10.1002/ana.21067.
To assess whether parasite infection is correlated with a reduced number of exacerbations and altered immune reactivity in multiple sclerosis (MS).
A prospective, double-cohort study was performed to assess the clinical course and radiological findings in 12 MS patients presenting associated eosinophilia. All patients presented parasitic infections with positive stool specimens. In all parasite-infected MS patients, the eosinophilia was not present during the 2 previous years. Eosinophil counts were monitored at 3- to 6-month intervals. When counts became elevated, patients were enrolled in the study. Interleukin (IL)-4, IL-10, IL-12, transforming growth factor (TGF)-beta, and interferon-gamma production by myelin basic protein-specific peripheral blood mononuclear cells were studied using enzyme-linked immunospot (ELISPOT). FoxP3 and Smad7 expression were studied by reverse-transcriptase polymerase chain reaction.
During a 4.6-year follow-up period, parasite-infected MS patients showed a significantly lower number of exacerbations, minimal variation in disability scores, as well as fewer magnetic resonance imaging changes when compared with uninfected MS patients. Furthermore, myelin basic protein-specific responses in peripheral blood showed a significant increase in IL-10 and TGF-beta and a decrease in IL-12 and interferon-gamma-secreting cells in infected MS patients compared with noninfected patients. Myelin basic protein-specific T cells cloned from infected subjects were characterized by the absence of IL-2 and IL-4 production, but high IL-10 and/or TGF-beta secretion, showing a cytokine profile similar to the T-cell subsets Tr1 and Th3. Moreover, cloning frequency of CD4+CD25+ FoxP3+ T cells was substantially increased in infected patients compared with uninfected MS subjects. Finally, Smad7 messenger RNA was not detected in T cells from infected MS patients secreting TGF-beta.
Increased production of IL-10 and TGF-beta, together with induction of CD25+CD4+ FoxP3+ T cells, suggests that regulatory T cells induced during parasite infections can alter the course of MS.
评估寄生虫感染是否与多发性硬化症（MS）病情加重次数减少及免疫反应性改变相关。
进行了一项前瞻性双队列研究，以评估12例伴有嗜酸性粒细胞增多的MS患者的临床病程和影像学表现。所有患者粪便标本寄生虫感染检测均呈阳性。在所有寄生虫感染的MS患者中，前两年均无嗜酸性粒细胞增多情况。每隔3至6个月监测嗜酸性粒细胞计数。当计数升高时，患者纳入本研究。使用酶联免疫斑点法（ELISPOT）研究髓鞘碱性蛋白特异性外周血单个核细胞产生白细胞介素（IL）-4、IL-10、IL-12、转化生长因子（TGF）-β和干扰素-γ的情况。通过逆转录聚合酶链反应研究FoxP3和Smad7的表达。
在4.6年的随访期内，与未感染的MS患者相比，寄生虫感染的MS患者病情加重次数显著减少，残疾评分变化极小，磁共振成像改变也较少。此外，与未感染患者相比，感染的MS患者外周血中髓鞘碱性蛋白特异性反应显示IL-10和TGF-β显著增加，而IL-12和分泌干扰素-γ的细胞减少。从感染受试者克隆的髓鞘碱性蛋白特异性T细胞的特征是不产生IL-2和IL-4，但IL-10和/或TGF-β分泌量高，显示出与Tr1和Th3 T细胞亚群相似的细胞因子谱。此外，与未感染的MS受试者相比，感染患者中CD4+CD25+FoxP3+T细胞的克隆频率大幅增加。最后，在分泌TGF-β的感染MS患者的T细胞中未检测到Smad7信使核糖核酸。
IL-10和TGF-β产生增加，以及CD25+CD4+FoxP3+T细胞的诱导，表明寄生虫感染期间诱导的调节性T细胞可改变MS的病程。
