Raj S, Nair S, Mastorakos G, Nelson L M
Department of Obstetrics and Gynecology, Louisiana State University Medical Center, New Orleans, USA.
Am J Reprod Immunol. 1995 Aug;34(2):125-31. doi: 10.1111/j.1600-0897.1995.tb00928.x.
Neonatal thymectomy performed on day 3 of life (NTX3) induces autoimmune oophoritis and ovarian failure in B6A mice. These mice develop high-titer autoantibodies specific to oocytes, and ultimately the ovaries become fibrotic and devoid of primordial follicles. These findings implicate the oocyte as a primary target of the autoimmune process. However, in previous work we demonstrated that in developing disease the lymphocytic infiltration was confined to the stroma and theca, and not found involving oocytes. Here, we investigate the possibility that lymphocytic infiltration involving oocytes develops as part of end-stage disease.
We transplanted normal syngeneic ovaries to B6A mice with confirmed autoimmune ovarian failure, and, as a control, to normal oophorectomized mice. We then defined the time course and histologic distribution of lymphocytic infiltration in the transplanted ovaries. Lymphocytes were identified by morphology with the aid of an immunohistochemical leukocyte marker (CD45).
Autoimmune oophoritis developed by 7 days after transplantation to the NTX3 mice. Compared to control mice, in these mice we found significantly increased stromal and thecal lymphocytic infiltration. In no case did we observe lymphocytic infiltration involving oocytes.
Our findings agree with our previous report and suggest that the ovarian failure in this model is not mediated by a direct lymphocytic attack against intact oocytes. Other immune-mediated mechanisms are responsible. The paradoxical development of high-titer oocyte-specific antibodies despite the stromal and thecal location of the lymphocytic infiltration remains to be explained.
在出生后第3天进行新生儿胸腺切除术（NTX3）会诱发B6A小鼠发生自身免疫性卵巢炎和卵巢功能衰竭。这些小鼠会产生针对卵母细胞的高滴度自身抗体，最终卵巢会发生纤维化且没有原始卵泡。这些发现表明卵母细胞是自身免疫过程的主要靶点。然而，在之前的研究中我们证明，在疾病发展过程中，淋巴细胞浸润局限于基质和卵泡膜，未发现涉及卵母细胞。在此，我们研究淋巴细胞浸润涉及卵母细胞是否作为终末期疾病的一部分而发生。
我们将正常同基因卵巢移植到已确诊自身免疫性卵巢功能衰竭的B6A小鼠以及作为对照的正常卵巢切除小鼠体内。然后我们确定了移植卵巢中淋巴细胞浸润的时间进程和组织学分布。借助免疫组织化学白细胞标志物（CD45）通过形态学鉴定淋巴细胞。
移植到NTX3小鼠后7天出现自身免疫性卵巢炎。与对照小鼠相比，在这些小鼠中我们发现基质和卵泡膜的淋巴细胞浸润显著增加。我们在任何情况下都未观察到淋巴细胞浸润涉及卵母细胞。
我们的发现与我们之前的报告一致，表明该模型中的卵巢功能衰竭不是由淋巴细胞对完整卵母细胞的直接攻击介导的。其他免疫介导机制起作用。尽管淋巴细胞浸润位于基质和卵泡膜，但高滴度卵母细胞特异性抗体的矛盾产生仍有待解释。
