Combination of gene delivery and DNA vaccination to protect from and reverse Th1 autoimmune disease via deviation to the Th2 pathway

被引:128
作者
Garren, H
Ruiz, PJ
Watkins, TA
Fontoura, P
Nguyen, LVT
Estline, ER
Hirschberg, DL
Steinman, L [1 ]
机构
[1] Stanford Univ, Beckman Ctr Mol Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA
[2] SunVax Corp, Palo Alto, CA 94304 USA
关键词
D O I
10.1016/S1074-7613(01)00171-6
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Using a combination of local gene delivery and tolerizing DNA vaccination, we demonstrate that codelivery of the interieukin-4 (IL-4) gene and a DNA vaccine encoding the self-peptide proteolipid protein 139-151 (PLP139-151) provides protective immunity against experimental autoimmune encephalomyelitis (EAE). We provide evidence for a mechanism whereby IL-4 expressed from the naked DNA is secreted and acts locally on autoreactive T cells via activation of STAT6 to shift their cytokine profile to T helper 2. We also show that DNA vaccines can be used to reverse established EAE by covaccination with the genes for myelin oligodendrocyte glycoprotein and IL-4. This treatment strategy combines the antigen-specific effects of DNA vaccination and the beneficial effects of local gene delivery.
引用
收藏
页码:15 / 22
页数:8
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