Neonatal injection of an ovarian peptide induces autoimmune ovarian disease in female mice: requirement of endogenous neonatal ovaries.

Neonatal female mice injected with the self ZP3 peptide are not tolerant to the peptide; they develop autoimmune ovarian disease (AOD) and autoantibody response 5 weeks later. ZP3 challenge leads to severe AOD and ZP3-specific T cell and antibody responses. In contrast, neonatal tolerance to foreign ZP3 peptide is established in male mice: ZP3 peptide-specific T cell proliferative response is reduced and AOD is absent in ovarian grafts. Tolerance is associated with a Th2-dominant T cell cytokine and antibody isotype profiles. As controls, neonatal tolerance to foreign peptides, with Th2 deviation, was induced in both male and female mice. Endogenous ZP3 is important for the gender difference. Ablation of ovaries in female mice on days 2 and 5, but not on day 7 or 14, switches the ZP3 autoimmune response to a tolerogenic response with a concomitant change in cytokine profile. Thus, neonatal self ZP3 peptide, supported by endogenous ovaries within a neonatal time window, evokes a pathogenic autoimmune response.