Critical role for adaptive T cell immunity in experimental eosinophilic esophagitis in mice.
We have previously developed a murine model of allergen-induced eosinophilic esophagitis (EE), characterized by intraepithelial eosinophils, extracellular granule deposition, and epithelial cell hyperplasia, features that mimic the pathophysiological changes observed in individuals with various forms of EE. We now test the hypothesis that adaptive T cell immunity is critical in initiating experimental EE. We first demonstrate that EE induction is associated with an increase in lymphocyte subpopulations (B+, CD4+, and CD8+ cells) in the esophagus. We induced experimental EE in wild-type and various lymphocyte subpopulation-deficient mice by intranasal allergen sensitization. Eosinophil levels and epithelial cell proliferation were determined by performing antimajor basic protein and antiproliferation cell nuclear antigen immunohistochemical analysis. Eosinophil accumulation in the esophagus was ablated completely in RAG1 gene-deficient mice, but no role for B cells or antigen-specific antibodies was found, as B cell-deficient (IgH6) mice developed unabated, experimental EE. In addition, T cell-deficient (forkhead box N1-/-) mice were protected from the induction of experimental EE. CD8alpha-deficient mice developed unaltered, experimental EE, and CD4-deficient mice were only protected moderately from disease induction. Taken together, these studies indicate a role for CD4+ and CD4- cell populations in EE pathogenesis and demonstrate that experimental allergen-induced EE is dependent on adaptive T cell immunity.
Mishra
Anil
A
Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, College of Medicine, OH 45229, USA.
Schlotman
James
J
Wang
Meiqin
M
Rothenberg
Marc E
ME
D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000139:chemically induced; D004804:Eosinophils / Q000276:immunology*; D004847:Epithelial Cells / Q000473:pathology; D004941:Esophagitis / Q000139:chemically induced / Q000276:immunology*; D004947:Esophagus / Q000473:pathology; D005260:Female; D006965:Hyperplasia; D007111:Immunity, Cellular; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*
D000485:Allergens