Qu Ning, Terayama Hayato, Hirayanagi Yoshie, Kuramasu Miyuki, Ogawa Yuki, Hayashi Shogo, Hirai Shuichi, Naito Munekazu, Itoh Masahiro
Department of Anatomy, Tokyo Medical University, Tokyo 160-8402, Japan.
Department of Anatomy, Division of Basic Medical Science, Tokai University School of Medicine, Kanagawa, Japan.
J Reprod Immunol. 2017 Jun;121:11-16. doi: 10.1016/j.jri.2017.04.006. Epub 2017 Apr 27.
We previously showed that immunization of mice with syngeneic or allogeneic testicular germ cells (TGC) alone induces autoimmune inflammation in the testes without using any adjuvant. In the present study, we examined testicular autoimmune response against xenogenic TGC antigens in mice. The mice were immunized with murine, rat or guinea pig TGC and then the histopathology, delayed type hypersensitivity (DTH) response and humoral autoimmunity were investigated. The results showed that immunization with not only murine but also rat TGC caused experimental autoimmune orchitis (EAO) with hypospermatogenesis in mice, while that with guinea pig TGC could not. The DTH response to murine TGC was significantly elevated in mice that had been immunized with murine or rat but not guinea pig TGC. Serum autoantibody to murine TGC was immunohistochemically detected in the mice immunized with either murine, rat or guinea pig TGC, however, the level of autoantibody detected by ELISA revealed significant elevation when mice were immunized with murine and rat TGC. With the immunoblotting after electrophoresis, the murine TGC proteins at molecular masses around 55kDa and 70kDa can be detected when incubated with sera from m-TGC and r-TGC groups. These results represent the cross-reactivity among TGC of the mouse, the rat and the guinea pig at the levels of humoral immunity and also demonstrate that the rat TGC could elicit significant DTH response to murine TGC with the resultant EAO. This is the first to succeed in EAO induction by the use of xenogenic TGC.
我们之前表明,仅用同基因或异基因睾丸生殖细胞(TGC)免疫小鼠,无需使用任何佐剂就能在睾丸中诱导自身免疫性炎症。在本研究中,我们检测了小鼠针对异种TGC抗原的睾丸自身免疫反应。用小鼠、大鼠或豚鼠的TGC免疫小鼠,然后研究其组织病理学、迟发型超敏反应(DTH)和体液自身免疫。结果表明,不仅用小鼠TGC免疫,用大鼠TGC免疫也会在小鼠中引发实验性自身免疫性睾丸炎(EAO)并伴有精子发生减少,而用豚鼠TGC免疫则不会。在用小鼠或大鼠而非豚鼠TGC免疫的小鼠中,对小鼠TGC的DTH反应显著升高。在用小鼠、大鼠或豚鼠TGC免疫的小鼠中,通过免疫组织化学检测到了针对小鼠TGC的血清自身抗体,然而,ELISA检测到的自身抗体水平在小鼠用小鼠和大鼠TGC免疫时显著升高。电泳后进行免疫印迹时,用m - TGC组和r - TGC组的血清孵育时,可检测到分子量约为55kDa和70kDa的小鼠TGC蛋白。这些结果表明,在体液免疫水平上,小鼠、大鼠和豚鼠的TGC之间存在交叉反应,也证明大鼠TGC能引发对小鼠TGC的显著DTH反应并导致EAO。这是首次成功利用异种TGC诱导出EAO。