Functional alteration of peripheral CD25(+)CD4(+)immunoregulatory T cells in a transgenic rat model of autoimmune diseases.
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.
Higuchi
Masato
M
Department of Pathology/Pathophysiology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan.
Ishizu
Akihiro
A
Ikeda
Hitoshi
H
Hayase
Hiroko
H
Fugo
Kazunori
K
Tsuji
Muneharu
M
Abe
Asami
A
Sugaya
Toshiaki
T
Suzuki
Akira
A
Takahashi
Toshiyuki
T
Koike
Takao
T
Yoshiki
Takashi
T
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
D015704:CD4 Antigens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2