Presentation of αB-crystallin to T cells in active multiple sclerosis lesions:: An early event following inflammatory demyelination
Presentation of αB-crystallin to T cells in active multiple sclerosis lesions:: An early event following inflammatory demyelination
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DOI：
10.4049/jimmunol.164.8.4359
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发表时间：
2000-04-15
影响因子：
4.4
通讯作者：
van Noort, JM
中科院分区：
文献类型：
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作者：
Bajramovic, JJ;Plomp, AC;van Noort, JM
在多发性硬化症 (MS) 的发展过程中，髓磷脂衍生的 Ags 对浸润性 T 细胞的（重新）激活被认为是关键的一步。此前，α B-晶状体蛋白已被证明是人类 T 细胞的重要髓磷脂 Ag。由于 α B 晶状体蛋白是一种细胞内热休克蛋白，因此问题是，在多发性硬化症病变发展过程中，该抗原在哪个阶段（如果有的话）可用于 CD4(+) T 细胞。在 10 个活动性多发性硬化症病变中，有 3 个可在血管周围巨噬细胞的吞噬小泡内检测到 α B 晶状体蛋白，与髓磷脂碱性蛋白和髓磷脂少突胶质细胞糖蛋白共定位(MOG)，尽管吞噬体中 MOG 的可检测性被认为是近期脱髓鞘的标志物，但与 α B-晶状体蛋白相比，在更多巨噬细胞和更多病变中检测到 MOG。体外研究证实，在 MOG 之前，巨噬细胞中的 α B-晶状体蛋白就已消失；髓鞘质摄取后 6 小时内，α B-晶状体蛋白从吞噬体中消失。含有 α B-晶状体蛋白的巨噬细胞与浸润性 T 细胞共定位，其特征是表达 MHC II 类、CD40 和 CD80。为了检查髓磷脂 Ag 向 T 细胞的功能呈递，纯化的巨噬细胞在体外用全髓磷脂膜进行脉冲。这些巨噬细胞在增殖和IFN-γ分泌方面激活了髓磷脂引发的T细胞和αB晶状体蛋白引发的T细胞。此外，αB晶状体蛋白脉冲的巨噬细胞激活髓磷脂引发的T细胞的程度与髓磷脂脉冲的巨噬细胞相同，而髓磷脂碱性蛋白脉冲的巨噬细胞根本不触发任何反应。这些数据表明，在活动性多发性硬化症病变中，αB-晶状体蛋白可在炎症脱髓鞘早期向 T 细胞进行功能性呈递。
In the development of multiple sclerosis (MS), (re)activation of infiltrating T cells by myelin-derived Ags is considered to be a crucial step, Previously, alpha B-crystallin has been shown to be an important myelin Ag to human T cells. Since alpha B-crystallin is an intracellular heat shock protein, the question arises at what stage, if any, during lesional development in MS this Ag becomes available for CD4(+) T cells, In 3 of 10 active MS lesions, alpha B-crystallin could be detected inside phagocytic vesicles of perivascular macrophages, colocalizing with myelin basic protein and myelin oligodendrocyte glycoprotein (MOG), Although the detectability of MOG in phagosomes is considered as a marker for very recent demyelination, MOG was detected in more macrophages and in more lesions than alpha B-crystallin. The disappearance of alpha B-crystallin from macrophages even before MOG was confirmed by in vitro studies; within 6 h after myelin-uptake alpha B-crystallin disappears from the phagosomes. alpha B-Crystallin-containing macrophages colocalized with infiltrating T cells and they were characterized by expression of MHC class II, CD40, and CD80, To examine functional presentation of myelin Ags to T cells, purified macrophages were pulsed in vitro with whole myelin membranes. These macrophages activated both myelin-primed and alpha B-crystallin-primed T cells in terms of proliferation and IFN-gamma secretion, In addition, alpha B-crystallin-pulsed macrophages activated myelin-primed T cells to the same extent as myelin-pulsed macrophages, whereas myelin basic protein-pulsed macrophages triggered no response at all. These data indicate that, in active MS lesions, alpha B-crystallin is available for functional presentation to T cells early during inflammatory demyelination.