A One Year Follow-Up Study of Natural Killer and Dendritic Cells Activities in Multiple Sclerosis Patients Receiving Glatiramer Acetate (GA)
A One Year Follow-Up Study of Natural Killer and Dendritic Cells Activities in Multiple Sclerosis Patients Receiving Glatiramer Acetate (GA)
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DOI：
10.1371/journal.pone.0062237
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发表时间：
2013-04-22
期刊：
影响因子：
3.7
通讯作者：
Maghazachi, Azzam A.
中科院分区：
文献类型：
--
作者：
Hoglund, Rune A.;Holmoy, Trygve;Maghazachi, Azzam A.
背景：多发性硬化（MS）是一种慢性炎症、脱髓鞘和神经退行性疾病。它被认为是由CD4（+）Th1/Th17细胞介导的。最近，先天免疫系统的细胞如树突状细胞（DC）和自然杀伤（NK）细胞已成为焦点。醋酸格拉替雷（GA）是一个批准的药物治疗MS patients.Methodology/主要发现：在目前的研究中，我们研究了NK和DC的活动在9复发缓解MS患者长达一年后开始GA治疗。我们观察到从这些患者中分离的NK细胞对K562细胞的细胞毒活性增加。进一步的分析显示，相同的NK细胞裂解自体未成熟DC（i）和成熟DC（m）。在大多数患者中，这种增加的活性与NK细胞活化细胞毒性受体（如NKp30、NKp44、NKp46和NKG2D）的增加以及这些NK细胞表面上抑制性分子CD158的表达减少相关。在大多数患者中，iDC和mDC上HLA-DR的表达增加，但未观察到HLA-I或HLA-E的表达的一致性。此外，在大多数情况下，共刺激受体CD80、CD83或CD86在iDC和mDC上的表达下调。此外，CCR6的表达在治疗的较晚时间点（32 - 48周之间）在mDCs上增加。结论/意义：我们的结果是第一次显示GA治疗对MS患者NK细胞的影响，这可能会影响将来使用这种药物和其他药物治疗这种疾病。
Background: Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease. It is thought to be mediated by CD4(+) Th1/Th17 cells. More recently, cells of the innate immune system such as dendritic cells (DCs) and natural killer (NK) cells have been in focus. Glatiramer acetate (GA) is an approved drug for treating MS patients.Methodology/Principal Findings: In the current study we examined the activities of NK and DCs in nine relapsing remitting MS patients for up to one year after initiation of GA treatment. We observed that NK cells isolated from most of these patients have increased cytotoxic activity against K562 cells. Further analysis showed that the same NK cells lysed both autologous immature (i) and mature (m) DCs. In most patients this increased activity was correlated with increased NK cell activating cytotoxicity receptors such as NKp30, NKp44, NKp46 and NKG2D, and reduced expression of the inhibitory molecule CD158 on the surface of these NK cells. The expression of HLA-DR was increased on iDCs and mDCs in the majority of the patients, but no consistency was observed for the expression of HLA-I or HLA-E. Also, the co-stimulatory receptors CD80, CD83 or CD86 expression was down-regulated on iDCs and mDCs in most cases. Further, the expression of CCR6 was increased on mDCs at later time points of therapy (between 32-48 weeks).Conclusions/Significance: Our results are the first showing the effects of GA treatment on NK cells in MS patients, which may impact future use of this and other drugs to treat this disease.