Department of Medical Biology, Faculty of Health Sciences, Jagiellonian University College of Medicine, Krakow, Poland.
Int Arch Allergy Immunol. 2014;164(2):122-36. doi: 10.1159/000363446. Epub 2014 Jun 28.
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 cells producing TGF-β. The aim of this study was to investigate the role of innate immunity in the suppression of CHS.
Mice were immunized by applying gauze patches containing protein antigen alone or in the presence of zymosan, and were then tested for the CHS response. Adoptive cell transfer experiments were used to study the mechanisms involved in the reversal of skin-induced suppression. The 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 trinitrophenyl chloride sensitization reverses skin-induced suppression, demonstrated in vivo and in vitro. The reversal of skin-induced suppression was transferable by antigen-specific TCRαβ+ CD4+ T contrasuppressor 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 the immunogenicity of weakly immunogenic antigens.
我们之前的工作表明，在半抗原致敏前，通过贴片形式对蛋白抗原（例如 TNP 结合的小鼠免疫球蛋白（TNP-Ig））进行表皮（EC）免疫，可以抑制小鼠 Th1 介导的接触超敏反应（CHS）。我们还发现，CHS 的抑制是由产生 TGF-β的 TCRαβ+CD4+CD8+T 抑制性细胞介导的。本研究旨在探讨固有免疫在抑制 CHS 中的作用。
通过在含有蛋白抗原的纱布贴片中进行免疫，或者在存在酵母聚糖的情况下进行免疫，然后对 CHS 反应进行测试。采用过继细胞转移实验研究逆转皮肤诱导抑制的机制。通过 ELISA 测量 EC 免疫对淋巴结细胞产生细胞因子的影响。
我们发现，在三硝基氯苯致敏前，用 TNP-Ig 和酵母聚糖进行 EC 免疫可以逆转体内和体外的皮肤诱导抑制。皮肤诱导抑制的逆转可以通过抗原特异性 TCRαβ+CD4+T 逆抑制性 T 细胞转移。此外，我们表明，这种逆抑制依赖于 IL-17A，并且与 TLR2 和 MyD88 无关。
我们的工作强烈表明，用蛋白抗原和酵母聚糖进行 EC 免疫可以逆转皮肤诱导的抑制，这种方法可能是增加弱免疫原性抗原免疫原性的潜在工具。
