Bagavant Harini, Sharp Colin, Kurth Barbara, Tung Kenneth S K
Department of Pathology, University of Virginia, Charlottesville, Virginia 22908, USA.
Am J Pathol. 2002 Jan;160(1):141-9. doi: 10.1016/S0002-9440(10)64358-1.
Autoimmune ovarian disease (AOD) is a probable cause of human premature ovarian failure, and a potential complication of contraceptive vaccines based on ovarian antigens. The diagnosis depends on detection of noninfectious ovarian inflammation (oophoritis) and serum antibody to ovarian and placental antigens. Mechanisms underlying AOD have been investigated in mice but not in primates. Herein, we report induction of AOD in primates, and compare the immunopathology between monkey and murine AOD. Four cynomolgus macaques immunized with monkey or human zona pellucida 3 peptide (pZP3) in adjuvant, developed T-cell responses to the immunizing peptide and produced antibody that bound to native zona pellucida in vivo. Immunostaining of ovaries from pZP3-immunized macaques showed numerous clusters of T cells co-localized with major histocompatibility complex II-positive macrophages in the ovarian interstitium. Such foci were not detected in untreated or adjuvant-treated control monkeys. This finding is comparable to murine pZP3-induced AOD. However, unlike murine AOD in which numerous granulomatous lesions are detected, severe granulomatous inflammation was detected in only one of three monkeys with abnormal immunohistology. Similar to mice with pZP3-induced AOD, the immunized monkeys retained normal ovarian function. The results are discussed in the context of complications of ZP-based human immunocontraceptive vaccines and case reports of human autoimmune oophoritis.
自身免疫性卵巢疾病（AOD）可能是人类卵巢早衰的一个原因，也是基于卵巢抗原的避孕疫苗的一种潜在并发症。诊断依赖于检测非感染性卵巢炎症（卵巢炎）以及针对卵巢和胎盘抗原的血清抗体。AOD的潜在机制已在小鼠中进行了研究，但在灵长类动物中尚未开展。在此，我们报告了在灵长类动物中诱导出AOD，并比较了猴和鼠AOD的免疫病理学。四只食蟹猴用佐剂中的猴或人透明带3肽（pZP3）进行免疫，产生了针对免疫肽的T细胞反应，并产生了在体内与天然透明带结合的抗体。对pZP3免疫的猕猴卵巢进行免疫染色显示，在卵巢间质中有大量T细胞簇与主要组织相容性复合体II阳性巨噬细胞共定位。在未处理或佐剂处理的对照猕猴中未检测到此类病灶。这一发现与鼠pZP3诱导的AOD相当。然而，与检测到大量肉芽肿性病变的鼠AOD不同，在免疫组织学异常的三只猕猴中，只有一只检测到严重的肉芽肿性炎症。与pZP3诱导的AOD小鼠相似，免疫的猕猴保留了正常的卵巢功能。将结合基于透明带的人类免疫避孕疫苗的并发症以及人类自身免疫性卵巢炎的病例报告对结果进行讨论。
