Transcutaneous immunization with cholera toxin B subunit adjuvant suppresses IgE antibody responses via selective induction of Th1 immune responses

Transcutaneous immunization with cholera toxin B subunit adjuvant suppresses IgE antibody responses via selective induction of Th1 immune responses
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DOI:
10.4049/jimmunol.170.3.1586
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发表时间:
2003-02-01
影响因子:
4.4
通讯作者:
Czerkinsky, C
Czerkinsky, C
中科院分区:
医学2区
文献类型:
--
作者:
Anjuère, F;George-Chandy, A;Czerkinsky, C

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局部应用霍乱毒素(CT)到小鼠皮肤上可以诱导对CT和共给药Ags的体液免疫反应。在这项研究中,我们检测了CT (CTB)的无毒细胞结合B亚基(CTB)与原型蛋白Ag, OVA共给药时作为皮肤免疫反应的潜在佐剂。应用于皮肤的CTB诱导血清对自身的抗体反应,其强度与CT引起的反应相当,但在促进对共给药OVA的全身抗体反应方面效率较低。然而,CT或CTB和OVA的经皮免疫(TCI)导致强烈的OVA特异性T细胞增殖反应。此外,CTB增强了Th1驱动的反应(ifn - γ产生),而CT诱导了Th1和Th2细胞因子的产生。毒性亚基CTA与CTB和OVA Ag共同给药,导致Th1和Th2反应增强。此外,虽然TC1和CT增强了血清IgE对共给药OVA的反应,但CTB抑制了这些反应。CT或CTB的TC1导致暴露的表皮和真皮中树突状细胞的积累增加。因此,与CT相比,经皮给药与粘膜给药的CTB表现出非常不同的行为,结果表明,CT对TC1诱导的Th1和th2依赖性反应的辅助作用分别涉及两个不同的部分,B和a亚基。中华免疫学杂志,2003,17(4):559 - 559。
Topical application of cholera toxin (CT) onto mouse skin can induce a humoral immune response to CT as well as to coadministered Ags. In this study, we examined the nontoxic cell-binding B subunit of CT (CTB) as a potential adjuvant for cutaneous immune responses when coadministered with the prototype protein Ag, OVA. CTB applied onto skin induced serum Ab responses to itself with magnitudes comparable to those evoked by CT but was poorly efficient at promoting systemic Ab responses to coadministered OVA. However, transcutaneous immunization (TCI) with either CT or CTB and OVA led to vigorous OVA-specific T cell proliferative responses. Furthermore, CTB potentiated Th1-driven responses (IFN-gamma production) whereas CT induced both Th1 and Th2 cytokine production. Coadministration of the toxic subunit CTA, together with CTB and OVA Ag, led to enhanced Th1 and Th2 responses. Moreover, whereas TC1 with CT enhanced serum IgE responses to coadministered OVA, CTB suppressed these responses. TC1 with either CT or CTB led to an increased accumulation of dendritic cells in the exposed epidermis and the underlying dermis. Thus, in contrast to CT, CTB appears to behave very differently when given by the transcutaneous as opposed to a mucosal route and the results suggest that the adjuvanticity of CT on Th1- and Th2-dependent responses induced by TC1 involves two distinct moieties, the B and the A subunits, respectively. The Journal of Immunology, 2003, 170: 1586-1592.