POST-THYMECTOMY MURINE EXPERIMENTAL AUTOIMMUNE OOPHORITIS IS ASSOCIATED WITH REDUCED NATURAL-KILLER-CELL ACTIVITY

PROBLEM: Natural killer (NK) cells can influence the immune response b y secreting potent lymphokines. It has been suggested that NK cells ha ve a suppressive action on B cells, and that impaired NK cell activity may play a role in some types of autoimmunity. NK cell abnormalities have been reported in women with premature ovarian failure. We therefo re examined NK cell activity during the development of murine experime ntal autoimmune oophoritis, which serves as a model for autoimmune ova rian failure in women. METHOD OF STUDY: Neonatally thymectomized and s ham-operated C57Bl/6 x A/J (B6A) mice were prepared and sacrificed at 4, 6, 8, and 10 weeks after surgery. Splenic NK cell activity was dete rmined in groups of five or more mice by measuring the percent specifi c lysis of target YAC-1 lymphoma cells using a standard 4-hr chromium release cytotoxicity assay. The number of splenic NK cells in neonatal ly thymectomized and sham-operated animals was also compared using flo w cytometry. In a subsequent experiment, interleukin 12 (IL-12; NK cel l-stimulating factor) was administered to neonatal mice before neonata l thymectomy. RESULTS: Neonatally thymectomized mice with associated a utoimmune oophoritis had a 75% reduction in the number of splenic NK c ells, and 50% or greater reduction in splenic NK cell activity at 4, 6 , and 8 weeks after surgery. IL-12 treatment before neonatal thymectom y maintained NK cell activity and was shown to ameliorate the associat ed autoimmune oophoritis. CONCLUSION: Murine post-thymectomy autoimmun e oophoritis is associated with reduced NK cell number and impaired NK cell activity, and in these respects the model is similar to prematur e ovarian failure in women. Research to define the relationship betwee n NK cell abnormalities and the mechanism of ovarian failure in this m odel might lend insight into the pathogenesis of premature ovarian fai lure in women.