Nyström-Asklin J, Adamsson J, Harandi A M
Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
Scand J Immunol. 2008 May;67(5):431-40. doi: 10.1111/j.1365-3083.2008.02085.x. Epub 2008 Feb 21.
The present study was carried out to test the immunostimulatory and adjuvant effects of the non-toxic B subunit of cholera toxin (CTB), CpG oligodeoxynucleotide (ODN) and CpG ODN linked to CTB (CTB-CpG) for generation of immunity against H. pylori in mice. Herein, we showed that CTB-CpG induces more potent proinflammatory cytokine and chemokine responses in the cervical and the mesenteric lymph nodes (CLN and MLN, respectively) cells in vitro compared with those of CTB and CpG ODN. The adjuvant effects of these agents were examined following intranasal immunization of C57Bl/6 mice with H. pylori lysate in combination with CpG ODN, CTB or CTB-CpG. All three immunization regimes resulted in high H. pylori-specific IgG antibody responses; however, only the CTB-CpG and, to some extent, the CpG ODN immunized mice mounted a sustainable IgG2c antibody response. Importantly, mice immunized with H. pylori antigen and CTB-CpG or CpG ODN, but not CTB, developed strong H. pylori-specific proliferative and IFN-gamma responses in their MLN CD4+ T cells upon recall antigen stimulation in vitro. These mice also had significantly lower bacterial load compared with the control-infected mice. Furthermore, the CTB-CpG and the CpG ODN immunized mice developed increased specific IgA antibody responses in their gastrointestinal tracts following H. pylori challenge. These results imply that CTB-CpG and CpG ODN, but not CTB, could serve as nasal adjuvants for induction of a H. pylori-specific Th1 type immunity in MLN and also a specific mucosal IgA antibody response in the gastrointestinal tract upon H. pylori challenge.
本研究旨在测试霍乱毒素（CTB）无毒B亚基、CpG寡脱氧核苷酸（ODN）以及与CTB相连的CpG ODN（CTB-CpG）对小鼠抗幽门螺杆菌免疫的免疫刺激和佐剂作用。在此，我们表明，与CTB和CpG ODN相比，CTB-CpG在体外可诱导宫颈和肠系膜淋巴结（分别为CLN和MLN）细胞产生更强的促炎细胞因子和趋化因子反应。在用幽门螺杆菌裂解物与CpG ODN、CTB或CTB-CpG联合对C57Bl/6小鼠进行鼻内免疫后，检测了这些试剂的佐剂作用。所有三种免疫方案均导致了高幽门螺杆菌特异性IgG抗体反应；然而，只有CTB-CpG以及在一定程度上CpG ODN免疫的小鼠产生了可持续的IgG2c抗体反应。重要的是，在用幽门螺杆菌抗原和CTB-CpG或CpG ODN免疫但未用CTB免疫的小鼠中，体外再次抗原刺激后，其MLN CD4+ T细胞产生了强烈的幽门螺杆菌特异性增殖和IFN-γ反应。与对照感染小鼠相比，这些小鼠的细菌载量也显著更低。此外，CTB-CpG和CpG ODN免疫的小鼠在幽门螺杆菌攻击后，其胃肠道中产生了增加的特异性IgA抗体反应。这些结果表明，CTB-CpG和CpG ODN而非CTB可作为鼻内佐剂，用于在MLN中诱导幽门螺杆菌特异性Th1型免疫，并在幽门螺杆菌攻击后在胃肠道中诱导特异性黏膜IgA抗体反应。
