Augmentation of natural immunity to a proinflammatory cytokine (TNF-alpha) by targeted DNA vaccine confers long-lasting resistance to experimental autoimmune encephalomyelitis

被引:33
作者
Wildbaum, G [1 ]
Karin, N [1 ]
机构
[1] Technion Israel Inst Technol, Bruce Rappaport Fac Med, Rappaport Family Inst Res Med Sci, Dept Immunol, IL-31096 Haifa, Israel
基金
以色列科学基金会;
关键词
TNF-alpha; DNA vaccination; natural immunity; neutralizing antibodies; experimental autoimmune encephalomyelitis; CNS;
D O I
10.1038/sj.gt.3300915
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
TNF-alpha is thought to be a key pro-inflammatory cytokine in T cell-mediated autoimmune diseases, particularly in rheumatoid arthritis (RA) and multiple sclerosis (MS). Experimental autoimmune encephalomyelitis (EAE) serves as an animal model for MS. The current study observes a notable TNF-alpha-specific antibody titer generated during the course of EAE, apparently not sufficient to prevent the development of disease. Administration of TNF-alpha-naked DNA vaccine enhanced the production of TNF-alpha-specific antibody titer and conferred EAE resistance. These antibodies were found to be neutralizing in vitro and capable of inhibiting the development of disease when transferred to other EAE rats. Thus, modulation of EAE with TNF-alpha DNA vaccines enhances the regulation of natural immunity to a self proinflammatory cytokine and provides a tool by which the immune system is encouraged to elicit anti-self protective immunity to restrain its own harmful reactivity when such a response is needed.
引用
收藏
页码:1128 / 1138
页数:11
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