Preferential induction of a Th-1 immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization
Preferential induction of a Th-1 immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization
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DOI：
10.1073/pnas.93.10.5141
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发表时间：
1996-05-14
影响因子：
11.1
通讯作者：
Carson, DA
中科院分区：
文献类型：
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作者：
Raz, E;Tighe, H;Carson, DA
我们比较了用大肠杆菌β-半乳糖苷酶（β-gal）或巨细胞病毒表达载体（pCMV-LacZ）中编码β-gal的质粒DNA（pDNA）皮内免疫的BALB/c小鼠中CD4（+）T细胞的抗原特异性抗体同种型和淋巴因子分泌。 pCMV-LacZ 主要诱导 IgG2a，而盐水或明矾中的 β-gal 诱导 IgG1 和 IgE β-gal 特异性抗体。此外，从 pDNA 免疫小鼠中分离的脾 CD4(+) T 辅助 (Th) 细胞分泌干扰素 γ，但不分泌白细胞介素 (IL)-4 和 IL-5，而来自注射 β-gal 的小鼠的 Th 细胞在体外用抗原刺激后，分泌 IL-4 和 IL-5，但不分泌干扰素 γ。这些数据共同表明，pDNA 免疫诱导了对相同抗原的 1 型辅助 T (Th-1) 反应，而蛋白质免疫则诱导了 2 型辅助 T (Th-2) 反应。有趣的是，用 pCMV-LacZ 引发小鼠可防止后续腹腔注射中 IgE 抗体的形成。明矾注射液中的β-半乳糖。这种效应是抗原特异性的，因为用 pCMV-LacZ 引发不会抑制 IgE 抗卵清蛋白抗体的形成。最重要的是，在明矾引发的小鼠中，用β-gal的pCMV-LacZ（但不是pCMV-OVA）皮内免疫导致IgE抗β-gal效价在6周内降低了66-75%。此外，在明矾引发的小鼠中，pCMV-LacZ 诱导 β-gal 中 Th 细胞特异性 IgG2a 抗体滴度和干扰素-γ 分泌。数据表明，基因免疫诱导的 Th-1 反应以抗原特异性方式主导了正在进行的蛋白质诱导的 Th-2 反应。这表明用编码过敏原的pDNA进行免疫可能为过敏性疾病提供一种新型的免疫疗法。
We compared the antigen-specific antibody isotypes and lymphokine secretion by CD4(+) T cells in BALB/c mice immunized intradermally with either Escherichia coli beta-galactosidase (beta-gal) or plasmid DNA (pDNA) encoding beta-gal in a cytomegalovirus-based expression vector (pCMV-LacZ). pCMV-LacZ induced mainly IgG2a, whereas beta-gal in saline or alum induced IgG1 and IgE beta-gal-specific antibodies. In addition, splenic CD4(+) T helper (Th) cells isolated from pDNA-immunized mice secreted interferon-gamma but not interleukin (IL)-4 and IL-5, whereas Th cells from beta-gal-injected mice secreted IL-4 and IL-5 but not interferon-gamma after in vitro stimulation with antigen. Together these data demonstrate that pDNA immunization induced a T helper type 1 (Th-1) response, whereas protein immunization induced a T helper type 2 (Th-2) response to the same antigen. Interestingly, priming of mice with pCMV-LacZ prevented IgE antibody formation to a subsequent i.p. beta-gal in alum injection. This effect was antigen-specific, because priming with pCMV-LacZ did not inhibit IgE anti-ovalbumin antibody formation. Most importantly, intradermal immunization with pCMV-LacZ (but not pCMV-OVA) of beta-gal in alum-primed mice caused a 66-75% reduction of the IgE anti-beta-gal titer in 6 weeks. Also, pCMV-LacZ induced specific IgG2a antibody titers and interferon-gamma secretion by Th cells in the beta-gal in alum-primed mice. The data demonstrate that gene immunization induces a Th-1 response that dominates over an ongoing protein-induced Th-2 response in an antigen-specific manner. This suggests that immunization with pDNA encoding for allergens may provide a novel type of immunotherapy for allergic diseases.