title: Functional alteration of peripheral CD25(+)CD4(+)immunoregulatory T cells in a transgenic rat model of autoimmune diseases.
abstract: Transgenic rats carrying the env-pX gene of human T cell leukemia virus type-I (env-pX rats) develop various collagen vascular diseases. Since autoantibodies are present in their sera, env-pX rats are considered to be a prototype model for autoimmune diseases. Adoptive transfers of spleen cells from syngenic non-transgenic rats decreased the incidence of diseases in env-pX rats, thus suggesting that normal spleen contains cells, which suppress autoimmune diseases. Murine peripheral CD25(+)CD4(+)T cells play roles in maintaining immunological self-tolerance. To examine if alterations of immunoregulatory cells may be evident in env-pX rats, quantitative and qualitative analyses of splenic CD25(+)CD4(+)T cells were done before these rats developed autoimmune diseases. Env-pX and non-transgenic rats had equivalent number of CD25(+)CD4(+)T cells. However, CD25(+)CD4(+)T cells from env-pX rats did not suppress proliferation of T cells stimulated by anti-CD3 antibodies (Ab) in vitro, whereas those from non-transgenic rats did. Additionally, env-pX CD25(+)CD4(+)T cells showed autologous and anti-CD3 Ab-mediated proliferation, in contrast to the anergic features in non-transgenic rats. These findings appear to be the first evidence that CD25(+)CD4(+)immunoregulatory T cells are altered in animal models, which naturally develop autoimmune diseases.
authors.affiliation: Department of Pathology/Pathophysiology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Higuchi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ishizu
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ikeda
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hayase
authors.forename: Kazunori
authors.initials: K
authors.lastname: Fugo
authors.forename: Muneharu
authors.initials: M
authors.lastname: Tsuji
authors.forename: Asami
authors.initials: A
authors.lastname: Abe
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sugaya
authors.forename: Akira
authors.initials: A
authors.lastname: Suzuki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshiki
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D007376:Interleukin-2 / Q000378:metabolism; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2