title: Homeostatically proliferating CD4 T cells are involved in the pathogenesis of an Omenn syndrome murine model.
abstract: Patients with Omenn syndrome (OS) have hypomorphic RAG mutations and develop varying manifestations of severe combined immunodeficiency. It is not known which symptoms are caused directly by the RAG mutations and which depend on other polymorphic genes. Our current understanding of OS is limited by the lack of an animal model. In the present study, we identified a C57BL/10 mouse with a spontaneous mutation in, and reduced activity of, RAG1. Mice bred from this animal contained high numbers of memory-phenotype T cells and experienced hepatosplenomegaly and eosinophilia, had oligoclonal T cells, and demonstrated elevated levels of IgE, major symptoms of OS. Depletion of CD4+ T cells in the mice caused a reduction in their IgE levels. Hence these "memory mutant" mice are a model for human OS; many symptoms of their disease were direct results of the Rag hypomorphism and some were caused by malfunctions of their CD4+ T cells.
authors.affiliation: Department of Developmental Immunology, Graduate School of Medicine and Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Khie
authors.initials: K
authors.lastname: Khiong
authors.forename: Masaaki
authors.initials: M
authors.lastname: Murakami
authors.forename: Chika
authors.initials: C
authors.lastname: Kitabayashi
authors.forename: Naoko
authors.initials: N
authors.lastname: Ueda
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Sawa
authors.forename: Akemi
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Brian L
authors.initials: BL
authors.lastname: Kotzin
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rozzo
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Ishihara
authors.forename: Marileila
authors.initials: M
authors.lastname: Verella-Garcia
authors.forename: John
authors.initials: J
authors.lastname: Kappler
authors.forename: Philippa
authors.initials: P
authors.lastname: Marrack
authors.forename: Toshio
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D007156:Immunologic Memory / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D018345:Mice, Knockout