title: Induction and immunohistology of autoimmune ovarian disease in cynomolgus macaques (Macaca fascicularis).
abstract: 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.
authors.affiliation: Department of Pathology, University of Virginia, Charlottesville, Virginia 22908, USA. hb5u@virginia.edu
authors.forename: Harini
authors.initials: H
authors.lastname: Bagavant
authors.forename: Colin
authors.initials: C
authors.lastname: Sharp
authors.forename: Barbara
authors.initials: B
authors.lastname: Kurth
authors.forename: Kenneth S K
authors.initials: KS
authors.lastname: Tung
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D004527:Egg Proteins / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization; D008252:Macaca fascicularis; D008262:Macrophage Activation; D008264:Macrophages / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009869:Oophoritis / Q000503:physiopathology; D010049:Ovarian Diseases / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D010053:Ovary / Q000473:pathology / Q000503:physiopathology; D011956:Receptors, Cell Surface; D013601:T-Lymphocytes / Q000473:pathology; D000072216:Zona Pellucida Glycoproteins
chemical_list: D001323:Autoantibodies; D004527:Egg Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000072216:Zona Pellucida Glycoproteins