Abstract |
Recent studies on autoimmune ovarian disease (AOD) induced by thymectomy on d3 (d3tx), and AOD induced by immunization with the ovary-specific zona pellucida 3 peptide (pZP3), have yielded the following results. First, female tolerance to pZP3 depends on the persistence of endogenous antigen (Ag). Second, following regulatory T-cell depletion, endogenous Ag in prepubertal d3tx mice triggers AOD and drives disease progression. Third, endogenous ZP3 from ovaries without AOD stimulates a diversified IgG autoantibody (autoAb) response that rapidly follows pZP3 T epitope immunization. Fourth, induction of AOD and autoimmune memory in neonatal female mice by pZP3 in incomplete Freund's adjuvant depends on endogenous Ag stimulation within the neonatal week. Fifth, in a rodent pinworm-positive environment, neonatal but not adult female mice injected with pZP3 in water develop Th2-mediated AOD and Th2 memory. Sixth, neonatal T cells transfer AOD to syngeneic athymic recipients, whereas adult T cells are non-pathogenic and in fact suppress AOD conferred by neonatal T cells. Therefore: 1) the continuous presence of physiologically-expressed autoAg is critical for both tolerance maintenance and autoimmune disease pathogenesis; the outcome is determined by the integrity of regulatory T cells; and 2) the neonatal mice, deficient in the regulatory T-cell function, are more responsive than adults to Ag and environmental stimuli that promote autoimmune disease and memory.
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Authors | K S Tung, S S Agersborg, P Alard, K M Garza, Y H Lou |
Journal | Immunological reviews
(Immunol Rev)
Vol. 182
Pg. 135-48
(Aug 2001)
ISSN: 0105-2896 [Print] England |
PMID | 11722630
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Review)
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Chemical References |
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Topics |
- Animals
- Animals, Newborn
(immunology, metabolism)
- Autoantigens
(immunology, metabolism)
- Autoimmune Diseases
(immunology, metabolism)
- Environment
- Female
- Male
- Ovarian Diseases
(immunology, metabolism)
- Ovary
(immunology, metabolism)
- T-Lymphocytes
(immunology)
- Thymectomy
- Thymus Gland
(cytology, immunology)
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