Role of inducible costimulator in the development of lupus in MRL/lpr mice.
Inducible costimulator (ICOS) is a costimulatory molecule expressed in activated T cells and plays an important role in T-cell-dependent immune responses. We investigated the role of ICOS in the development of autoimmune diseases in MRL/Mpj-lpr/lpr (MRL/lpr) mice. ICOS was expressed on CD4(+) T cells from adult MRL/lpr mice. ICOS-deficient MRL/lpr mice showed mild lymphoadenopathy and a decreased memory type CD4(+) T cells in the spleen. The anti-dsDNA antibody levels were decreased. CD4(+) T cells from ICOS-deficient MRL/lpr mice showed less of a bias to Th1 and an enhanced production of IL-4 in response to anti-CD3 antibody in comparison to those from wild-type MRL/lpr mice. Although ICOS-deficiency abrogated renal vasculitis completely, the severity of glomerulonephritis was not altered. ICOS is considered to play a role in CD4(+) T cell activation, autoantibody production, and renal vasculitis. However, it is not essentially required in the development of glomerulonephritis.
Tada
Yoshifumi
Y
Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan. taday@cc.saga-u.ac.jp
Koarada
Syuichi
S
Tomiyoshi
Yoshiyuki
Y
Morito
Fumitaka
F
Mitamura
Mio
M
Haruta
Yoshio
Y
Ohta
Akihide
A
Nagasawa
Kohei
K
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics* / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005921:Glomerulonephritis / Q000150:complications / Q000401:mortality; D007136:Immunoglobulins / Q000097:blood; D060889:Inducible T-Cell Co-Stimulator Protein; D007668:Kidney / Q000473:pathology; D008177:Lupus Vulgaris / Q000150:complications / Q000209:etiology* / Q000276:immunology; D008206:Lymphatic Diseases / Q000276:immunology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013163:Splenomegaly / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; C556694:Icos protein, mouse; D007136:Immunoglobulins; D060889:Inducible T-Cell Co-Stimulator Protein