Neutralizing antibodies to IFN-gamma-inducing factor prevent experimental autoimmune encephalomyelitis.
Neutralizing antibodies to IFN-gamma-inducing factor prevent experimental autoimmune encephalomyelitis.
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DOI：
10.4049/jimmunol.161.11.6368
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发表时间：
1998-12
影响因子：
4.4
通讯作者：
G. Wildbaum;S. Youssef;N. Grabie;N. Karin
中科院分区：
文献类型：
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作者：
G. Wildbaum;S. Youssef;N. Grabie;N. Karin
特异性寡核苷酸引物被用来识别和分离IFN-γ诱导因子（IGIF）从发展中的实验性自身免疫性脑脊髓炎（EAE），T细胞介导的自身免疫性疾病的中枢神经系统，作为多发性硬化症的模型大鼠的大脑。IGIF在EAE发病时和发病过程中在脑中高度转录。用PCR产物制备大鼠IGIF重组蛋白，诱导抗IGIF中和抗体。这些抗体显着减少了IFN-γ的生产，由引发的T细胞增殖响应其目标髓鞘碱性蛋白表位和Con A激活的T细胞从幼稚供体。当在活动性或转移性EAE的发展过程中给予大鼠时，这些抗体显著阻断了疾病的发展。将来自受保护大鼠的脾T细胞与致脑炎髓鞘碱性蛋白表位一起培养，并评估IL-4和IFN-γ的产生。这些增殖的细胞表现出IL-4产生的显著增加，伴随着IFN-γ和TNF-α产生的显著减少。因此，我们认为，干扰Th 1/Th 2平衡对Th 2细胞的EAE阻断抗IGIF免疫治疗的机制。
Specific oligonucleotide primers were used to identify and isolate IFN-gamma-inducing factor (IGIF) from the brain of rats with developing experimental autoimmune encephalomyelitis (EAE), a T cell-mediated autoimmune disease of the central nervous system that serves as a model for multiple sclerosis. IGIF was highly transcribed in the brain at the onset and during the course of active EAE. PCR products encoding rat IGIF were used to generate the recombinant protein that was used to induce anti-IGIF neutralizing Abs. These Abs significantly reduced the production of IFN-gamma by primed T cells proliferating in response to their target myelin basic protein epitope and by Con A-activated T cells from naive donors. When administered to rats during the development of either active or transferred EAE, these Abs significantly blocked the development of disease. Splenic T cells from protected rats were cultured with the encephalitogenic myelin basic protein epitope and evaluated for production of IL-4 and IFN-gamma. These cells, which proliferated, exhibited a profound increase in IL-4 production that was accompanied by a significant decrease in IFN-gamma and TNF-alpha production. Thus, we suggest that perturbation of the Th1/Th2 balance toward Th2 cells is the mechanism underlying EAE blockade by anti-IGIF immunotherapy.