A Study of the Regulation of Dendritic Cells and Immunological Memory by Immunoglobulins in Multiple Sclerosis

多发性硬化症中免疫球蛋白对树突状细胞和免疫记忆的调节研究

基本信息

批准号：
18590923
负责人：
FUJIHARA Kazuo
金额：
$ 2.43万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590923/
关键词：
Multiple Sclerosis Demyelinating Disease Immunoglobulin Dendritic Cell

项目摘要

Intravenous immunoglobulin preparations (IVIg) are reportedly effective in inhibiting the relapseof multiple sclerosis (MS), but few reports have investigated the effect of IVIg on dendritic cells (DCs), which are thought to be involved in such relapses. Using a system that uses monokines to differentiate DCs from peripheral blood monocytes (Mo-DCs), we investigated the effect of Immunoglobulin G (IgG) on these antigen-presenting cells. Treatment of monocytes derived from a healthy volunteer with IgG partially inhibited the expression of CD1a, a marker of immature DCs (imDCs), and CD40 and CD80, which are markers associated with T cell activation. In contrast, IgG treatment enhanced the expression of CD83, a marker of mature DCs (mDCs). IgG markedly inhibited the expression of CD49d [very late activation antigen (VLA)-4 〓4-integrin], the adhesion molecule required for mDCs to cross the blood brain barrier (BBB). As neutralizing antibodies against CD49d have a therapeutic effect on MS, we investigated the effect of IgG on Mo-DCs derived from the peripheral blood of relapsing-remitting MS patients. We obtained similar results in both MS patients and healthy controls. In addition, IgG treatment of cells from both healthy controls and MS patients inhibited the production of interleukin (IL)-12, a cytokine associated with mDC maturation, but did not inhibit the production of IL-10. These results suggested the possibility that IgG treatment, apart from its known ability to regulate inflammation, may help prevent relapses of MS by controlling DC maturation, consequently inhibiting invasion of the central nervous system and affecting the cytokine profile.

据报道，静脉注射免疫球蛋白制剂（IVIg）可有效抑制多发性硬化症（MS）的复发，但很少有报道研究IVIg对树突状细胞（DC）的影响，树突状细胞被认为与这种复发有关。为了将 DC 与外周血单核细胞 (Mo-DC) 区分开来，我们研究了免疫球蛋白 G (IgG) 对这些抗原呈递细胞的治疗作用。来自健康志愿者的单核细胞的 IgG 部分抑制了 CD1a（未成熟树突状细胞 (imDC) 的标记物）以及 CD40 和 CD80（与 T 细胞活化相关的标记物）的表达。成熟 DC (mDC) 的标志物 IgG 显着抑制 CD49d [极晚激活抗原 (VLA)-4〓4-整合素] 的表达，粘附。由于针对 CD49d 的中和抗体对 MS 具有治疗作用，我们研究了 IgG 对源自复发缓解型 MS 患者外周血的 Mo-DC 的作用。此外，对来自健康对照和 MS 患者的细胞进行 IgG 处理可抑制白细胞介素 (IL)-12（一种与 mDC 成熟相关的细胞因子）的产生，但不会抑制 mDC 成熟。这些结果表明，IgG 治疗除了具有调节炎症的已知能力外，还可能通过控制 DC 成熟来帮助预防 MS 复发，从而抑制中枢神经系统的侵袭并影响细胞因子谱。