Activation of natural killer T cells potentiates or prevents experimental autoimmune encephalomyelitis.
Activation of natural killer T cells potentiates or prevents experimental autoimmune encephalomyelitis.
复制标题
DOI：
10.1084/jem.194.12.1789
复制
发表时间：
2001-12-17
影响因子：
15.3
通讯作者：
Kumar, V
中科院分区：
文献类型：
--
作者：
Jahng, A W;Maricic, I;Pedersen, B;Burdin, N;Naidenko, O;Kronenberg, M;Koezuka, Y;Kumar, V
自然杀伤（NK）T细胞在主要组织相容性复合体（MHC）1类分子CD 1的背景下识别脂质抗原，并在T细胞受体（TCR）接合时快速分泌大量细胞因子干扰素（IFN）-γ和白细胞介素（IL）-4。我们已经问过NK T细胞活化是否会影响适应性T细胞对髓鞘抗原的反应，以及它们引起实验性自身免疫性脑脊髓炎（EAE）（多发性硬化症的一种模型）的能力。虽然用糖脂α-半乳糖神经酰胺（α-GalCer）和髓磷脂反应性T细胞同时激活NK T细胞可增强B10.PL小鼠的EAE，但预先激活NK T细胞可预防疾病。EAE的加重是由增强的1型辅助性T细胞（Th 1）对髓鞘碱性蛋白的反应介导的，并且在IFN-γ缺陷的小鼠中消失。保护作用由抗髓鞘碱性蛋白（MBP）应答的免疫偏离介导，并依赖于IL-4的分泌。α-GalCer的调节作用需要CD 1d抗原呈递途径，并取决于B10.PL或C57 BL/6小鼠中NK T细胞应答的性质。由于CD 1分子是非多态性的，并且在不同物种之间非常保守，因此NK T细胞活化的调节代表了T细胞介导的自身免疫性疾病的干预目标。
Natural killer (NK) T cells recognize lipid antigens in the context of the major histocompatibility complex (MHC) class 1–like molecule CD1 and rapidly secrete large amounts of the cytokines interferon (IFN)-γ and interleukin (IL)-4 upon T cell receptor (TCR) engagement. We have asked whether NK T cell activation influences adaptive T cell responses to myelin antigens and their ability to cause experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. While simultaneous activation of NK T cells with the glycolipid α-galactosylceramide (α-GalCer) and myelin-reactive T cells potentiates EAE in B10.PL mice, prior activation of NK T cells protects against disease. Exacerbation of EAE is mediated by an enhanced T helper type 1 (Th1) response to myelin basic protein and is lost in mice deficient in IFN-γ. Protection is mediated by immune deviation of the anti-myelin basic protein (MBP) response and is dependent upon the secretion of IL-4. The modulatory effect of α-GalCer requires the CD1d antigen presentation pathway and is dependent upon the nature of the NK T cell response in B10.PL or C57BL/6 mice. Because CD1 molecules are nonpolymorphic and remarkably conserved among different species, modulation of NK T cell activation represents a target for intervention in T cell–mediated autoimmune diseases.