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Innate IL-10 promotes the induction of Th2 responses with plasmid DNA expressing HIV gp120

机译：先天IL-10促进表达HIV gp120的质粒DNA诱导Th2反应

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摘要

Like most DNA vaccines, intramuscular immunization with plasmid DNA coding for influenza virus haemagglutinin (HApDNA) induced Th1 responses and IgG2a antibodies in mice. However, plasmid DNA coding for HIV gp120 (gp120pDNA) induced Th2-biased responses and predominantly IgG1 antibodies. Responses to gp120pDNA switched to a Th1-type in IL-10-defective mice and to exclusively IgG2a antibodies in IL-4-defective mice. Conversely, antigen-specific IFN-gamma production induced by gp120pDNA or HApDNA was reduced in IL-12-defective mice, whereas addition of plasmid DNA coding for IL-12 enhanced Th1 responses. Plasmid DNA stimulated IL-10 and IL-12 production by macrophages and dendritic cells (DCs) in vitro and anti-IL-10 antibodies enhanced IL-12 production and DC maturation in response to gp120pDNA. Our findings suggest that T cell responses induced by DNA vaccines is influenced by the nature of the antigen, and that the induction of Th2-biased responses with gp120pDNA is mediated in part through the stimulation of innate IL-10, which inhibits activation of DCs that direct the induction of Th1 cells.
机译：与大多数DNA疫苗一样，用编码流感病毒血凝素（HApDNA）的质粒DNA进行肌肉内免疫可诱导小鼠Th1反应和IgG2a抗体。但是，编码HIV gp120（gp120pDNA）的质粒DNA诱导了偏向Th2的应答，并且主要是IgG1抗体。在IL-10缺陷小鼠中，对gp120pDNA的反应转换为Th1型，而在IL-4缺陷小鼠中，仅对IgG2a抗体转换。相反，在IL-12缺陷型小鼠中，由gp120pDNA或HApDNA诱导的抗原特异性IFN-γ产生减少，而添加编码IL-12的质粒DNA则增强了Th1应答。质粒DNA在体外刺激巨噬细胞和树突状细胞（DC）刺激IL-10和IL-12的产生，抗IL-10抗体响应gp120pDNA增强IL-12的产生和DC成熟。我们的发现表明，DNA疫苗诱导的T细胞反应受抗原性质的影响，而gp120pDNA诱导的Th2偏向反应的诱导部分是通过先天IL-10的刺激介导的，后者可抑制DC的激活，指导Th1细胞的诱导。

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