title: A convenient model of severe, high incidence autoimmune gastritis caused by polyclonal effector T cells and without perturbation of regulatory T cells.
abstract: Autoimmune gastritis results from the breakdown of T cell tolerance to the gastric H(+)/K(+) ATPase. The gastric H(+)/K(+) ATPase is responsible for the acidification of gastric juice and consists of an α subunit (H/Kα) and a β subunit (H/Kβ). Here we show that CD4(+) T cells from H/Kα-deficient mice (H/Kα(-/-)) are highly pathogenic and autoimmune gastritis can be induced in sublethally irradiated wildtype mice by adoptive transfer of unfractionated CD4(+) T cells from H/Kα(-/-) mice. All recipient mice consistently developed the most severe form of autoimmune gastritis 8 weeks after the transfer, featuring hypertrophy of the gastric mucosa, complete depletion of the parietal and zymogenic cells, and presence of autoantibodies to H(+)/K(+) ATPase in the serum. Furthermore, we demonstrated that the disease significantly affected stomach weight and stomach pH of recipient mice. Depletion of parietal cells in this disease model required the presence of both H/Kα and H/Kβ since transfer of H/Kα(-/-) CD4(+) T cells did not result in depletion of parietal cells in H/Kα(-/-) or H/Kβ(-/-) recipient mice. The consistency of disease severity, the use of polyclonal T cells and a specific T cell response to the gastric autoantigen make this an ideal disease model for the study of many aspects of organ-specific autoimmunity including prevention and treatment of the disease.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Eric
authors.initials: E
authors.lastname: Tu
authors.forename: Desmond K Y
authors.initials: DK
authors.lastname: Ang
authors.forename: Thea V
authors.initials: TV
authors.lastname: Hogan
authors.forename: Simon
authors.initials: S
authors.lastname: Read
authors.forename: Cheryl P Z
authors.initials: CP
authors.lastname: Chia
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gleeson
authors.forename: Ian R
authors.initials: IR
authors.lastname: van Driel
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000209:etiology / Q000276:immunology*; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D013270:Stomach / Q000473:pathology; D050378:T-Lymphocytes, Regulatory
chemical_list: D017506:H(+)-K(+)-Exchanging ATPase
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