A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing TH2 bias of natural killer T cells
A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing TH2 bias of natural killer T cells
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DOI：
10.1038/35097097
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发表时间：
2001-10-04
期刊：
影响因子：
64.8
通讯作者：
Yamamura, T
中科院分区：
文献类型：
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作者：
Miyamoto, K;Miyake, S;Yamamura, T
实验性自身免疫性脑脊髓炎（EAE）是一种由1型辅助T（T（H）1）细胞介导并受调节细胞控制的原型自身免疫性疾病（1-3）。在这里，我们报告了一种合成的糖脂配体，用于表达半恒定T细胞受体（V α 14（+））的CD 1d限制性自然杀伤T（NKT）细胞，可预防EAE。该配体是α-半乳糖基神经酰胺（α-GC）的类似物，其为原型NKT细胞配体，具有截短的鞘氨醇链。α-GC使NKT细胞产生干扰素（IFN）-γ和白细胞介素（IL）-4（参考文献4，5）。然而，这种新的配体可以诱导NKT细胞主要产生IL-4。单次注射这种糖脂，而不是α-GC，通过引起NKT细胞产生IL-4，持续诱导自身免疫T细胞的T（H）2偏向，导致EAE的抑制。缺乏CD 1d的多态性以及小鼠和人NKT细胞对相同配体的交叉反应性应答（6）表明，用该配体靶向NKT细胞可能是干预人类自身免疫性疾病如多发性硬化症的有吸引力的手段。
Experimental autoimmune encephalomyelitis (EAE) is a prototype autoimmune disease mediated by type 1 helper T (T(H)1) cells and under the control of regulatory cells(1-3). Here we report that a synthetic glycolipid ligand for CD1d-restricted natural killer T (NKT) cells expressing the semi-invariant T-cell receptor (V alpha 14(+)) is preventive against EAE. The ligand is an analogue of alpha -galactosylceramide (alpha -GC), a prototype NKT cell ligand, with a truncated sphingosine chain. alpha -GC causes NKT cells to produce both interferon (IFN)-gamma and interleukin (IL)-4 (refs 4, 5). However, this new ligand can induce a predominant production of IL-4 by the NKT cells. A single injection of this glycolipid, but not of alpha -GC, consistently induced T(H)2 bias of autoimmune T cells by causing NKT cells to produce IL-4, leading to suppression of EAE. The lack of polymorphism of CD1d and cross-reactive response of mouse and human NKT cells to the same ligand(6) indicates that targeting NKT cells with this ligand may be an attractive means for intervening in human autoimmune diseases such as multiple sclerosis.