Caput epididymitis but not orchitis was induced by vasectomy in a murine model of experimental autoimmune orchitis
Caput epididymitis but not orchitis was induced by vasectomy in a murine model of experimental autoimmune orchitis
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DOI：
10.1530/rep-08-0018
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发表时间：
2008-06-01
期刊：
影响因子：
3.8
通讯作者：
Itoh, Masahiro
中科院分区：
文献类型：
--
作者：
Qu, Ning;Terayama, Hayato;Itoh, Masahiro
用同系睾丸生殖细胞（TGC）单独免疫小鼠可诱导针对圆形精子细胞和伸长精子细胞自身抗原的自身免疫反应，导致实验性自身免疫性睾丸炎（EAC）的发生。在这种没有佐剂的EAO模型中，组织学病变的特征是淋巴细胞浸润到睾丸中，生精障碍和完全没有附睾炎。在这项研究中，我们研究了输精管结扎术（Vx）对TG诱导的EAO的影响，期望Vx增加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显著的炎性细胞反应，而接受shamVx+TGC免疫的小鼠具有EAO而无附睾炎。与此形成鲜明对比的是，在接受Vx + TGC免疫的任何小鼠的睾丸中均未发现EAO。相反，在它们中诱导了涉及CD 4 + T细胞、CD 8 + T细胞、B细胞和巨噬细胞的附睾头炎，同时IL 6和IL 10 mRNA的组织水平显著升高。此外，shamVx + TGC免疫诱导的血清自身抗体与圆形（未成熟）和伸长（成熟）精子细胞反应;然而，Vx+TGC免疫诱导的那些特异性成熟精子细胞和精子的顶体。这些意想不到的结果表明，VX可以诱导的模式，其中自身反应性淋巴细胞获得获得TGC自身抗原的附睾，导致自身免疫反应对自身抗原的成熟，而不是不成熟的精子细胞。
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 (EAC). 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 IL 10 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.