Cutting edge:: Vα14-Jα281 NKT cells naturally regulate experimental autoimmune encephalomyelitis in nonobese diabetic mice
Cutting edge:: Vα14-Jα281 NKT cells naturally regulate experimental autoimmune encephalomyelitis in nonobese diabetic mice
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DOI：
10.4049/jimmunol.168.12.6007
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发表时间：
2002-06-15
影响因子：
4.4
通讯作者：
Liblau, RS
中科院分区：
文献类型：
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作者：
Mars, LT;Laloux, W;Liblau, RS
尽管在多发性硬化症和易患实验性自身免疫性脑脊髓炎（EAE）的小鼠品系中观察到NKT细胞群的缺陷，但对这些细胞在中枢神经系统自身免疫中的功能知之甚少。在这项工作中，我们报道了TCR Valpha14-Jalpha281转基因非肥胖糖尿病小鼠，富集cd1限制性NKT细胞，免受EAE的保护。这种保护与脾脏中ag特异性ifn - γ产生的显著抑制有关，这意味着对脑致生Th1反应的调节。这种调节与IL-4无关，因为IL-4缺陷的Valpha14-Jalpha281小鼠仍然可以抵抗EAE，并且与NKT细胞驱动的Th1向Th2的偏离无关，因为在免疫的Valpha14-Jalpha281转基因小鼠中没有观察到增加的自身抗原特异性Th2反应。我们的研究结果表明，富集和/或刺激cd1依赖性NKT细胞可能被用作治疗中枢神经系统自身免疫的新策略。
Although deficiencies in the NKT cell population have been observed in multiple sclerosis and mouse strains susceptible to experimental autoimmune encephalomyelitis (EAE), little is known about the function of these cells in CNS autoimmunity. In this work we report that TCR Valpha14-Jalpha281 transgenic nonobese diabetic mice, which are enriched in CD1d-restricted NKT cells, are protected from EAE. The protection is associated with a striking inhibition of Ag-specific IFN-gamma production in the spleen, implying modulation of the encephalitogenic Th1 response. This modulation is independent of IL-4 because IL-4-deficient Valpha14-Jalpha281 mice are still protected against EAE and independent of NKT cell-driven Th1 to Th2 deviation, because no increased autoantigen-specific Th2 response was observed in immunized Valpha14-Jalpha281 transgenic mice. Our findings indicate that enrichment and/or stimulation of CD1d-dependent NKT cells may be used as a novel strategy to treat CNS autoimmunity.