DNA immunization to prevent autoimmune diabetes
DNA immunization to prevent autoimmune diabetes
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DOI：
10.1172/jci7209
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发表时间：
1999-07-01
影响因子：
15.9
通讯作者：
von Herrath, MG
中科院分区：
文献类型：
--
作者：
Coon, B;An, LL;von Herrath, MG
表达淋巴细胞性脉络膜脑膜炎病毒核蛋白(LCMV-NP)的小鼠只有在LCMV感染后才会发生胰岛素依赖型糖尿病(IDDM)。在该模型中，接种编码胰岛素B链的质粒DNA可使IDDM的发病率降低50%。胰岛素B链DNA疫苗通过诱导调节性的CD4淋巴细胞与胰岛素B链反应，分泌IL-4，并在胰腺引流淋巴结局部降低LCMV-NP自身反应性细胞毒性T淋巴细胞的活性而有效。相反，用表达LCMV病毒(“自身”)蛋白的质粒进行类似的疫苗接种并不能预防IDDM，因为没有诱导出这样的调节细胞。因此，用表达自身抗原的质粒进行DNA免疫可能成为预防自身免疫性疾病的一种新的和有吸引力的治疗方法，如果抗原被仔细地预先选择以在体内诱导调节性淋巴细胞的能力的话。
Mice expressing lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP) as a transgene in their beta cells develop insulin-dependent diabetes mellitus (IDDM) only after LCMV infection. Inoculation of plasmid DNA encoding the insulin B chain reduced the incidence of IDDM by 50% in this model. The insulin B-chain DNA vaccination was effective through induction of regulatory CD4 lymphocytes that react with the insulin B chain, secrete IL-4, and locally reduce activity of LCMV-NP-autoreactive cytotoxic T lymphocytes in the pancreatic draining lymph node. In contrast, similar vaccination with plasmids expressing the LCMV viral ("self") protein did not prevent IDDM, because no such regulatory cells were induced. Thus, DNA immunization with plasmids expressing self-antigens might constitute a novel and attractive therapeutic approach to prevent autoimmune diseases, if the antigens are carefully preelected for an ability to induce regulatory lymphocytes in vivo.