Musha Muhetaerjiang, Hirai Shuichi, Naito Munekazu, Terayama Hayato, Qu Ning, Hatayama Naoyuki, Itoh Masahiro
Department of Anatomy, Tokyo Medical University, Tokyo 160-8402, Japan.
J Reprod Dev. 2013;59(2):139-44. doi: 10.1262/jrd.2012-121. Epub 2012 Dec 17.
Experimental autoimmune orchitis (EAO) is a model of immunologic male infertility and pathologically characterized by lymphocytic inflammation, which causes breakdown of the testicular immune privilege with spermatogenic disturbance. Generally, murine EAO is induced by immunization with testicular homogenate (TH) from the testes of donor mice + complete Freund's adjuvant (CFA) + Bordetella pertussigens (BP), and it has been considered that treatment with these two adjuvants is required to enhance the immune response against testicular antigens. However, there remains a possibility that CFA and BP may affect autoimmune responses against the testicular antigens without TH. In the present study, we examined this possibility using real-time RT-PCR, Western blotting and immunohistochemical staining. The results demonstrated that immunization with TH in combination with CFA and BP evoked more severe EAO than that with only TH. Real-time RT-PCR analyses revealed that Fas mRNA expression in TH+CFA+BP-induced EAO was significantly higher than that in TH-induced EAO. Interestingly, IL-6 mRNA expression dramatically increased in TH+CFA+BP-induced EAO; however, no apparent change in IL-6 mRNA expression occurred in TH-induced EAO. It was also noted that treatment with CFA and BP alone augmented autoimmune reactions against some testicular autoantigens. These results indicates that these adjuvants are helpful in evoking severe EAO, and treatment with the adjuvants alone can evoke autoimmune reactions against some testicular autoantigens despite the use of no TH.
实验性自身免疫性睾丸炎(EAO)是一种免疫性男性不育模型,其病理特征为淋巴细胞炎症,可导致睾丸免疫豁免权破坏并伴有生精障碍。一般来说,小鼠EAO是通过用供体小鼠睾丸的睾丸匀浆(TH)+完全弗氏佐剂(CFA)+百日咳博德特氏菌(BP)进行免疫诱导的,并且一直认为需要用这两种佐剂来增强针对睾丸抗原的免疫反应。然而,仍有可能CFA和BP在没有TH的情况下也会影响针对睾丸抗原的自身免疫反应。在本研究中,我们使用实时RT-PCR、蛋白质免疫印迹和免疫组织化学染色来研究这种可能性。结果表明,与仅用TH免疫相比,用TH联合CFA和BP免疫诱发的EAO更严重。实时RT-PCR分析显示,在TH+CFA+BP诱导的EAO中Fas mRNA表达明显高于TH诱导的EAO。有趣的是,在TH+CFA+BP诱导的EAO中IL-6 mRNA表达显著增加;然而,在TH诱导的EAO中IL-6 mRNA表达没有明显变化。还注意到单独用CFA和BP处理可增强针对某些睾丸自身抗原的自身免疫反应。这些结果表明,这些佐剂有助于诱发严重的EAO,并且单独使用佐剂治疗可诱发针对某些睾丸自身抗原的自身免疫反应,尽管未使用TH。