T Helper Cytokine Responses Induced by Nasal Immunization with Glucosyltransferase-I of Streptococcus sobrinus
T Helper Cytokine Responses Induced by Nasal Immunization with Glucosyltransferase-I of Streptococcus sobrinus
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DOI：
10.5466/ijoms.9.227
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发表时间：
2011
期刊：
影响因子：
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通讯作者：
Keita Watanabe;T. Hashizume;T. Kurita-Ochiai;Y. Akimoto;Masafumi Yamamoto
中科院分区：
文献类型：
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作者：
Keita Watanabe;T. Hashizume;T. Kurita-Ochiai;Y. Akimoto;Masafumi Yamamoto
我们以前的研究表明，用远缘链球菌产生的葡萄糖基转移酶-I（GTF-I）鼻腔免疫可激发血清IgG、血清伊加和唾液伊加抗体应答，从而提供对由链球菌引起的龋齿的保护。远缘感染在这项研究中，开发一种有效的疫苗，用于预防龋齿，我们评估了辅助性T细胞（Th）细胞反应时，全身和粘膜隔室的GTF-I鼻腔给药。当从单独用GTF-1或GTF-1加未甲基化胞嘧啶-磷酸-鸟嘌呤寡脱氧核苷酸（CpG ODN）免疫的小鼠的脾或颈淋巴结分离的CD 4 + T细胞在体外用GTF-1再刺激时，诱导显著水平的增殖反应。Th 1（IFN-γ）和Th 2（IL-4）细胞因子应答的分析显示，来自单独给予GTF-1的小鼠的GTF-1特异性Th细胞产生显著水平的IL-4和低IFN-γ。另一方面，与单独给予GTF-1的小鼠相比，给予GTF-1 + CpG ODN的小鼠的CD 4 + T细胞产生的IFN-γ水平增加，而IL-4的产生没有改变。IgG亚类应答证实了细胞因子谱，表明虽然鼻用GTF-1主要引发IgG 1抗体，但GTF-1加CpG ODN进一步增强IgG 2a和IgG 2b，但不增强IgG 1抗体应答。这些结果表明，用GTF-1鼻内免疫在粘膜和全身淋巴组织中激发GTF-1特异性Th 2细胞因子应答，并且CpG ODN作为佐剂增强了对共同施用的GTF-1的Th 1型细胞因子应答。
Our previous study showed that nasal immunization with glucosyltransferase-I (GTF-I) produced by Streptococcus sobrinus elicits serum IgG, serum IgA, and salivary IgA antibody responses that provide protection against dental caries caused by S. sobrinus infection. In this study, to develop an effective vaccine for the prevention of dental caries, we assessed T helper (Th) cell responses in systemic and mucosal compartments when GTF-I was administered nasally. When CD4+ T cells isolated from the spleen or cervical lymph nodes of mice immunized with GTF-I alone or GTF-I plus unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN) were re-stimulated with GTF-I in vitro, significant levels of proliferative responses were induced. Analysis of Th1 (IFN-γ) and Th2 (IL-4) cytokine responses showed that GTF-I-specific Th cells from mice given GTF-I alone produced a significant level of IL-4 with low IFN-γ. On the other hand, CD4+ T cells from mice given GTF-I plus CpG ODN produced increased levels of IFN-γ when compared with those of mice given GTF-I alone, whereas the IL-4 production was not changed. The IgG subclass responses confirmed the cytokine profile, showing that while nasal GTF-I elicited mainly IgG1 antibodies, GTF-I plus CpG ODN further enhanced IgG2a and IgG2b, but not IgG1, antibody responses. These results suggest that nasal immunization with GTF-I elicits GTF-I-specific Th2 cytokine responses in both mucosal and systemic lymphoid tissues and that CpG ODN as an adjuvant enhances Th1-type cytokine responses to co-administered GTF-I.