Dendritic cells in multiple sclerosis lesions: Maturation stage, myelin uptake, and interaction with proliferating T cells
Dendritic cells in multiple sclerosis lesions: Maturation stage, myelin uptake, and interaction with proliferating T cells
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DOI：
10.1093/jnen/65.2.124
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发表时间：
2006-02-01
影响因子：
3.2
通讯作者：
Aloisi, F
中科院分区：
文献类型：
--
作者：
Serafini, B;Rosicarelli, B;Aloisi, F
在多发性硬化（MS）中，被募集到中枢神经系统（CNS）的树突状细胞（DC）被认为参与针对髓鞘抗原的自身免疫应答的调节。为了更好地了解DC在CNS炎症中的作用，我们对MS患者尸检脑组织中DC成熟标志物和DC与CNS浸润T细胞的关系进行了详细的免疫组化分析。我们还研究了MS病变中含有髓鞘碎片的DC的存在。使用以下标志物鉴定髓样DC亚群：用于未成熟DC的CD la;用于未成熟和成熟DC的DC-SIGN;以及用于成熟DC的成束蛋白、CD 83、DC-LAMP和CCR 7。最常见的发现是在早期活动性和慢性（活动性和非活动性）MS病变的血管周围袖中存在表达DC-SIGN并含有髓鞘成分的细胞。在10例MS患者中，仅1例在活动性病变中检测到血管周围CD1a（+）DC。尽管数量少于DC-SIGN（+）DC，但表达成熟DC标志物的细胞在检查的大多数活动性病变的炎症脑膜和血管周围袖中一致地检测到。CCR7免疫染色主要局限于病变边缘的活化小胶质细胞。发现一些血管周围DC-SIGN（+）细胞靠近或接触罕见的增殖淋巴细胞，其中大多数表达DC-SIGN配体ICAM-3和CD8。这些数据表明，DC招募和成熟的MS病变，其中自身抗原是由连续的髓鞘破坏，可能有助于局部激活和扩展的可能致病的T细胞。
In multiple sclerosis (MS), dendritic cells (DCs) recruited to the central nervous system (CNS) are thought to be involved in the regulation of autoimmune responses directed against myelin antigens. To better understand the role of DCs in CNS inflammation, we performed a detailed immunohistochemical analysis of DC maturation markers and of DC relationship to CNS-infiltrating T cells in autopsy brain tissue of patients with MS. We also investigated the presence of DCs containing myelin debris in MS lesions. Myeloid DC subsets were identified using the following markers: CD 1 a for immature DCs; DC-SIGN for immature and mature DCs; and fascin, CD83, DC-LAMP, and CCR7 for mature DCs. The most common finding was the presence of cells expressing DC-SIGN and containing myelin components in the perivascular cuffs of early active and chronic (both active and inactive) MS lesions. Perivascular CD1a(+) DCs were detected in active lesions in only one of 10 patients with MS who were examined. Although less numerous than DC-SIGN(+) DCs, cells expressing mature DC markers were consistently detected in the inflamed meninges and perivascular cuffs of most active lesions examined. CCR7 immunostaining was predominantly confined to activated microglia at the lesion edges. Some perivascular DC-SIGN(+) cells were found in close proximity to or contacting rare proliferating lymphocytes, most of which expressed the DC-SIGN ligand ICAM-3 and CD8. These data suggest that DCs recruited and maturing in MS lesions, where self-antigens are made available by continuous myelin destruction, may contribute to the local activation and expansion of presumably pathogenic T cells.