Mucosal adjuvant effect of cholera toxin in mice results from induction of T helper 2 (Th2) cells and IL-4.
Mucosal adjuvant effect of cholera toxin in mice results from induction of T helper 2 (Th2) cells and IL-4.
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DOI：
10.4049/jimmunol.155.10.4621
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发表时间：
1995-11
影响因子：
4.4
通讯作者：
M. Marinaro;H. Staats;T. Hiroi;R. Jackson;M. Coste;P. Boyaka;N. Okahashi;M. Yamamoto;Hiroshi Kiyono;Horst Bluethmann;K. Fujihashi;Jerry R. McGhee
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文献类型：
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作者：
M. Marinaro;H. Staats;T. Hiroi;R. Jackson;M. Coste;P. Boyaka;N. Okahashi;M. Yamamoto;Hiroshi Kiyono;Horst Bluethmann;K. Fujihashi;Jerry R. McGhee
尽管霍乱毒素（CT）的病理生理作用，包括腹泻，是一个强大的粘膜免疫原和佐剂。我们研究了CT对辅助性T细胞（Th）1型（Th 1）和Th 2细胞调节的Ag特异性B细胞同种型和IgG亚类Ab反应的影响，当毒素与不同蛋白质Ag共同口服时引起。当用破伤风类毒素（TT）和CT作为佐剂口服免疫小鼠时，该方案诱导胃肠道中的TT特异性分泌型伊加应答以及血清IgG（包括IgG 1和IgG 2b亚类）和伊加应答。该口服方案还诱导TT-和CT-B-特异性IgE应答。此外，CT也引起了佐剂效应的Ag特异性IgG 1，IgE和伊加反应时，其他两种蛋白抗原，卵清蛋白和鸡蛋白色溶菌酶，通过口服途径。进行定量逆转录酶-PCR以评估TT刺激的CD 4 + T细胞培养物中Th 1（IFN-γ）和Th 2（IL-4）细胞因子表达的mRNA水平。派尔集合淋巴结和脾CD 4 + T细胞表达的IL-4特异性信息水平显著增加，但没有导致IFN-γ mRNA表达的变化。为了确定免疫途径是否影响IgE应答，将小鼠皮下免疫。以TT和CT为辅助。当CT联合给药时，诱导总IgE抗体和TT特异性IgE抗体显著增加。总之，这些结果表明CT作为粘膜佐剂增强Th 2型应答，特别是产生的IL-4导致与该细胞因子相关的特征性Ab同种型模式。
Despite pathophysiologic effects including diarrhea, cholera toxin (CT) is a potent mucosal immunogen and adjuvant. We investigated the influence of CT on T helper (Th)-type 1 (Th1) and Th2 cell-regulated Ag-specific B cell isotype and IgG subclass Ab responses elicited when the toxin was co-administered orally with different protein Ags. When mice were orally immunized with tetanus toxoid (TT) and CT as adjuvant, this regimen induced TT-specific secretory IgA responses in the gastrointestinal tract as well as serum IgG, including IgG1 and IgG2b subclasses, and IgA responses. This oral regimen also induced TT- and CT-B-specific IgE responses. In addition, CT also elicited adjuvant effects for Ag-specific IgG1, IgE, and IgA responses when two other protein Ags, OVA and hen egg white lysozyme, were given by the oral route. Quantitative reverse transcriptase-PCR was performed to assess levels of mRNA for Th1 (IFN-gamma) and Th2 (IL-4) cytokine expression in TT-stimulated CD4+ T cell cultures. Both Peyer's patches and splenic CD4+ T cells expressed markedly increased levels of IL-4-specific message, but did not result in changes in IFN-gamma mRNA expression. To determine whether the route of immunization influenced IgE responses, mice were immunized s.c. with TT and CT as adjuvant. Significant increases in total and TT-specific IgE Abs were induced when CT was co-administered. Taken together, these results show that CT acts as a mucosal adjuvant to enhance Th2-type responses and in particular, the IL-4 produced results in a characteristic Ab isotype pattern associated with this cytokine.