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Role of inducible costimulator in the development of lupus in MRL/lpr mice.

Tada Y, Koarada S, Tomiyoshi Y, Morito F, Mitamura M, Haruta Y, Ohta A, Nagasawa K

Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan. taday@cc.saga-u.ac.jp

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.

Published 25 July 2006 in Clin Immunol, 120(2): 179-88.
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