Department of Anatomy, Tokyo Medical University, Shinjuku 6-1-1, Shinjuku-ku, Tokyo 160-8402, Japan.
J Reprod Immunol. 2011 Aug;90(2):195-201. doi: 10.1016/j.jri.2011.03.008. Epub 2011 Jun 30.
Haploid germ cells (spermatids and spermatozoa) develop in the testis after immune tolerance has been established. Therefore, they contain various autoimmunogenic antigens, but the testis is known to be an immunologically privileged organ. In particular, the blood-testis barrier formed by Sertoli cells protects autoimmunogenic haploid germ cells from attack by the autoimmune system. Experimental autoimmune orchitis (EAO), a breakdown of the testicular immune privilege leading to immunological male infertility, has been ordinarily induced in mice by immunization twice with testicular antigens+complete Freund's adjuvant (CFA)+Bordetella pertussis (BP). We previously found that two subcutaneous injections of viable syngeneic testicular germ cells induced murine EAO without the use of CFA+BP. In both EAO models, the lesions are characterized by spermatogenic disturbance with lymphocytic inflammation, and a second immunization with testicular antigens is critical for the disease induction. In the present study, we found that only one placement of a syngeneic donor's testes, epididymides and vasa deferentia (TEV) into the abdominal cavity or subcutaneous space was sufficient to induce EAO on the recipient's testes in mice. It was also noted that the placement of TEV induced only orchitis without epididymo-vasitis, while the serum autoantibodies were reactive with haploid germ cells existing throughout the TEV. Furthermore, the TEV placed in the abdominal cavity rather than the subcutaneous space was effective in inducing severe EAO, and the A/J strain was most susceptible to the TEV-induced EAO among the three strains examined. The model of EAO induced by the placement of the donor's TEV into the abdominal cavity in A/J mice will be helpful for the further analyses of testicular autoimmunity.
单倍体生殖细胞(精母细胞和精子)在免疫耐受建立后在睾丸中发育。因此,它们含有各种自身免疫原性抗原,但睾丸被认为是一个免疫特惠器官。特别是,由支持细胞形成的血睾屏障保护自身免疫性单倍体生殖细胞免受自身免疫系统的攻击。实验性自身免疫性睾丸炎(EAO)是睾丸免疫特惠性的破坏,导致免疫性男性不育,通常通过用睾丸抗原+完全弗氏佐剂(CFA)+百日咳博德特氏菌(BP)两次免疫小鼠来诱导。我们之前发现,两次皮下注射活同基因睾丸生殖细胞可诱导小鼠 EAO,而无需使用 CFA+BP。在这两种 EAO 模型中,病变的特征是伴有淋巴细胞炎症的精子发生障碍,并且用睾丸抗原进行第二次免疫接种对于疾病诱导是关键的。在本研究中,我们发现仅将一个同基因供体的睾丸、附睾和输精管(TEV)放置在腹腔或皮下空间中足以在小鼠的受体睾丸上诱导 EAO。还注意到,TEV 的放置仅引起睾丸炎而没有附睾-输精管炎,而血清自身抗体与存在于 TEV 中的单倍体生殖细胞反应。此外,与放置在皮下空间相比,将 TEV 放置在腹腔中更有效地诱导严重的 EAO,并且在检查的三个品系中,A/J 品系对 TEV 诱导的 EAO 最敏感。将供体 TEV 放置在 A/J 小鼠腹腔中诱导 EAO 的模型将有助于进一步分析睾丸自身免疫。