Qu Ning, Terayama Hayato, Naito Munekazu, Ogawa Yuki, Hirai Shuichi, Kitaoka Miyuki, Yi Shuang-Qin, Itoh Masahiro
Department of Anatomy, Tokyo Medical University, Tokyo 160-8402, Japan.
Reproduction. 2008 Jun;135(6):859-66. doi: 10.1530/REP-08-0018.
Immunization of mice with viable syngeneic testicular germ cells (TGC) alone can induce autoimmune responses against autoantigens of both round and elongating spermatids, resulting in the development of experimental autoimmune orchitis (EAO). Histological lesions in this EAO model without an adjuvant are characterized by lymphocytic infiltration into the testes, spermatogenic disturbance, and a complete lack of epididymitis. In this study, we investigated the effects of vasectomy (Vx) on TGC-induced EAO expecting that Vx augments the severity of testicular inflammation in A/J mice. The results showed that mice receiving Vx alone exhibited no significant inflammatory cell response in either the testes or epididymides, and mice receiving shamVx+TGC immunization had EAO with no epididymitis. In sharp contrast, no EAO was found in the testes of any mice receiving Vx+TGC immunization. Instead, caput epididymitis involving CD4+T cells, CD8+T cells, B cells, and macrophages were induced in them with striking elevation of the tissue levels of both IL6 and IL10 mRNA. Furthermore, serum autoantibodies induced by shamVx+TGC immunization were reactive with both round (immature) and elongating (mature) spermatids; however, those induced by Vx+TGC immunization were specific to acrosomes of mature spermatids and spermatozoa. These unexpected results indicate that Vx may induce the mode by which autoreactive lymphocytes gain access to TGC autoantigens in the epididymides, leading to autoimmune responses against the autoantigens of mature rather than immature spermatids.
仅用活的同基因睾丸生殖细胞(TGC)对小鼠进行免疫接种,可诱导针对圆形和伸长型精子细胞自身抗原的自身免疫反应,从而导致实验性自身免疫性睾丸炎(EAO)的发生。在无佐剂的情况下,该EAO模型的组织学病变特征为淋巴细胞浸润睾丸、生精紊乱以及完全没有附睾炎。在本研究中,我们调查了输精管切除术(Vx)对TGC诱导的EAO的影响,期望Vx能加重A/J小鼠睾丸炎症的严重程度。结果显示,单独接受Vx的小鼠在睾丸或附睾中均未表现出明显的炎症细胞反应,接受假手术+TGC免疫接种的小鼠患有EAO且无附睾炎。与之形成鲜明对比的是,接受Vx+TGC免疫接种的任何小鼠睾丸中均未发现EAO。相反,它们诱导了涉及CD4+T细胞、CD8+T细胞、B细胞和巨噬细胞的附睾头附睾炎,同时IL6和IL10 mRNA的组织水平显著升高。此外,假手术+TGC免疫接种诱导的血清自身抗体与圆形(未成熟)和伸长型(成熟)精子细胞均有反应;然而,Vx+TGC免疫接种诱导的血清自身抗体则特异性针对成熟精子细胞和精子的顶体。这些意外结果表明,Vx可能诱导自身反应性淋巴细胞进入附睾中TGC自身抗原的模式,从而导致针对成熟而非未成熟精子细胞自身抗原的自身免疫反应。