Epicutaneous immunization with TNP-Ig and Zymosan induces TCRαβ+ CD4+ contrasuppressor cells that reverse skin-induced suppression via IL-17A.

Epicutaneous immunization with TNP-Ig and Zymosan induces TCRαβ+ CD4+ contrasuppressor cells that reverse skin-induced suppression via IL-17A.
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DOI:
10.1159/000363446
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发表时间:
2014
影响因子:
2.8
通讯作者:
Szczepanik M
Szczepanik M
中科院分区:
医学3区
文献类型:
--
作者:
Majewska-Szczepanik M;Strzepa A;Marcińska K;Wen L;Szczepanik M

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我们以前的工作表明,在半抗原致敏之前,用蛋白质抗原,如TNP结合的小鼠免疫球蛋白(TNP-Ig)以贴片的形式进行皮肤免疫(EC),可以抑制Th1介导的接触性超敏反应(CHS)。我们还发现,CHS的抑制是由产生αβ-β的TCRCD4+CD8+T抑制(TS)细胞介导的。本研究的目的是探讨先天免疫在抑制CHS中的作用。将含有蛋白质抗原的纱布贴片单独或在酵母多糖存在下免疫小鼠,然后检测CHS反应。过继细胞转移实验用于研究逆转皮肤诱导抑制的机制。采用ELISA法检测EC免疫对小鼠淋巴结细胞产生细胞因子的影响。我们发现,在TNP-Cl致敏之前用TNP-Ig和酵母多糖免疫EC可以逆转皮肤诱导的抑制,这在体内和体外都得到了证实。皮肤诱导的抑制的逆转可以通过抗原特异性的TCRCD4+T细胞来逆转。此外,我们还发现,这种逆转抑制依赖于IL-17A,而不依赖于TLR2和MyD88。我们的工作强烈表明,EC用蛋白抗原和酵母多糖免疫可以逆转皮肤诱导的抑制,这种方法可能是一种潜在的工具,可以提高每周免疫原性抗原的免疫原性。
Our previous work showed that epicutaneous (EC) immunization with protein antigen e.g. TNP-conjugated mouse immunoglobulin (TNP-Ig) in the form of a patch prior to hapten sensitization inhibits Th1-mediated contact hypersensitivity (CHS) in mice. We also found that suppression of CHS was mediated by TCRαβ+ CD4+ CD8+ T suppressor (Ts) cells producing TGF-β. The aim of the current study was to investigate the role of innate immunity in suppression of CHS. Mice were immunized by applying gauze patches containing protein antigen alone or in the presence of zymosan and then tested for CHS response. Adoptive cell transfer experiments were used to study mechanisms involved in reversal of skin-induced suppression. Influence of EC immunization on cytokine production by lymph node cells was measured by ELISA. We found that EC immunization with TNP-Ig and zymosan before TNP-Cl sensitization reverses skin-induced suppression as demonstrated in vivo and in vitro. The reversal of skin-induced suppression was transferable by antigen-specific TCRαβ+ CD4+ T contrasuppressor (Tcs) cells. Furthermore, we showed that the contrasuppression was IL-17A dependent and TLR2 and MyD88 independent. Our work strongly suggests that EC immunization with protein antigen and zymosan reverses skin-induced suppression and that this approach may be a potential tool to increase immunogenicity of weekly immunogenic antigens.
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