Coon B, An L L, Whitton J L, von Herrath M G
Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
J Clin Invest. 1999 Jul;104(2):189-94. doi: 10.1172/JCI7209.
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.
在β细胞中作为转基因表达淋巴细胞性脉络丛脑膜炎病毒核蛋白（LCMV-NP）的小鼠，仅在感染LCMV后才会发展为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疫苗接种通过诱导与胰岛素B链反应、分泌IL-4并在胰腺引流淋巴结中局部降低LCMV-NP自身反应性细胞毒性T淋巴细胞活性的调节性CD4淋巴细胞而发挥作用。相比之下，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，因为没有诱导出此类调节性细胞。因此，如果能仔细筛选出具有在体内诱导调节性淋巴细胞能力的抗原，那么用表达自身抗原的质粒进行DNA免疫可能构成一种预防自身免疫性疾病的新颖且有吸引力的治疗方法。
