Intestinal parasitism terminates self tolerance and enhances neonatal induction of autoimmune disease and memory.
Genetic and environmental factors both influence autoimmune disease occurrence, but the identity and mechanism of action of environmental factors are poorly understood. Here we show that pinworm-infected neonatal but not adult mice, injected with an ovarian self peptide of the zona pellucida protein 3 (pZP3) in water and without adjuvant, develop Th2 responses and severe eosinophilic autoimmune ovarian disease. A strong Th2 memory response is recalled when, as adults, the mice are challenged with a regimen that elicits a strong Th1 response in naive adults. The strong Th2 autoimmune response included high levels of IL-4 and IL-5 production by pZP3-specific T cells, and an IgG1-biased autoantibody response. The Th2 response ended promptly upon pinworm eradication, and partially resurfaced upon re-infection. We conclude that the rodent pinworm is an environmental agent that modifies the neonatal response to a self peptide, resulting in termination of the tolerance state and induction of a strong Th2-associated autoimmune disease and T cell memory.
Agersborg
S S
SS
Department of Microbiology, University of Virginia, Charlottesville 22908, USA.
Garza
K M
KM
Tung
K S
KS
D000818:Animals; D000831:Animals, Newborn; D000969:Antinematodal Agents / Q000494:pharmacology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004527:Egg Proteins / Q000276:immunology; D017229:Enterobiasis / Q000150:complications / Q000188:drug therapy; D004802:Eosinophilia / Q000469:parasitology / Q000473:pathology; D005260:Female; D005273:Fenbendazole / Q000494:pharmacology; D007156:Immunologic Memory; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009869:Oophoritis / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D011956:Receptors, Cell Surface; D017634:Self Tolerance; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014605:Uveitis / Q000276:immunology; D000072216:Zona Pellucida Glycoproteins
D000969:Antinematodal Agents; D001324:Autoantigens; D016207:Cytokines; D004527:Egg Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000072216:Zona Pellucida Glycoproteins; D005273:Fenbendazole