Antigen presentation in the CNS by myeloid dendritic cells drives progression of relapsing experimental autoimmune encephalomyelitis
Antigen presentation in the CNS by myeloid dendritic cells drives progression of relapsing experimental autoimmune encephalomyelitis
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DOI：
10.1196/annals.1394.023
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Bailey, Samantha L.
中科院分区：
文献类型：
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作者：
Miller, Stephen D.;McMahon, Eileen J.;Bailey, Samantha L.
多发性硬化症（MS）小鼠模型复发性实验性自身免疫性脑脊髓炎（R-EAE）的慢性进展依赖于T细胞对内源性髓磷脂表位的激活，即表位扩散。本文就表位扩散的细胞和分子机制作一综述。令人惊讶的是，在接受R-EAE的SJL小鼠中，幼稚T细胞对内源性髓磷脂表位的激活直接发生在中枢神经系统（CNS）中，这是一个通常被认为具有免疫特权的部位。对从R-EAE小鼠中枢神经系统纯化的抗原呈递细胞（APC）群体的抗原呈递能力的测定表明，外周来源的CD11b(+)CD11c(+)CD45 hi髓样树突状细胞（mDCs）最有效地呈递内源性髓鞘抗原，以激活预激活的效应髓鞘特异性T细胞和幼稚T细胞。驱动表位扩散的mDCs优先极化致病性Th17反应，这与它们增强的tgf - β 1、IL-6和IL-23的表达相关。B220(+)CD11c（+）浆细胞样细胞（pDCs）和CD8 α (+)CD11c(+) （CD8 DCs）均优于CD11b(+)CDI11c(-)CD45（hi）巨噬细胞，但在呈递内源性肽诱导Th17细胞的效率低于mDCs。相比之下，从炎症中枢神经系统中纯化的CNS驻留CD11b(+)CD11c(-)CD45（低）小胶质细胞被发现在很大程度上不能激活初始T细胞或效应T细胞。
Chronic progression of relapsing experimental autoimmune encephalomyelitis (R-EAE), a mouse model of multiple sclerosis (MS), is dependent on the activation of T cells to endogenous myelin epitopes, that is, epitope spreading. This review focuses on the cellular and molecular mechanisms underlying the process of epitope spreading. Surprisingly, activation of naive T cells to endogenous myelin epitopes in SJL mice undergoing R-EAE occurs directly in the central nervous system (CNS), a site generally perceived to be immunologically privileged. Determination of the antigen presentation capacity of antigen-presenting cell (APC) populations purified from the CNS of mice with established R-EAE shows that peripherally derived CD11b(+)CD11c(+)CD45 hi myeloid dendritic cells (mDCs) most efficiently present endogenous myelin antigens to activate both preactivated effector myelin-specific T cells and naive T cells. The mDCs, which drive epitope spreading, preferentially polarize pathogenic Th17 responses correlating with their enhanced expression of TGF-beta 1, IL-6, and IL-23. Both B220(+)CD11c(+) plasmacytoid (pDCs) and CD8 alpha(+)CD11c(+) (CD8 DCs) were superior to CD11b(+)CDI11c(-)CD45(hi) macrophages, but less efficient than mDCs at presenting endogenous peptide to induce Th17 cells. In contrast, CNS-resident CD11b(+)CD11c(-)CD45(low) microglia purified from the inflamed CNS were found to be largely incapable of activating either naive or effector T cells.