1. Role of 2B4-mediated signals in the pathogenesis of a murine hepatitis model independent of Fas and Vα14 NKT cells
- Author
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Mitsunobu Matsubara, Masato Nose, Hiroshi Furukawa, Hiroshi Kitazawa, Masao Ono, and Izumi Kaneko
- Subjects
CD4-Positive T-Lymphocytes ,Mice, Inbred MRL lpr ,Immunology ,Autoimmune hepatitis ,Biology ,CD8-Positive T-Lymphocytes ,urologic and male genital diseases ,Mice ,Signaling lymphocytic activation molecule ,Antigen ,immune system diseases ,Antigens, CD ,Signaling Lymphocytic Activation Molecule Family ,medicine ,Concanavalin A ,Immunology and Allergy ,Animals ,Immunologic Factors ,fas Receptor ,Receptors, Immunologic ,Receptor ,skin and connective tissue diseases ,Hepatitis ,Antibodies, Monoclonal ,Original Articles ,medicine.disease ,Natural killer T cell ,Mice, Mutant Strains ,Disease Models, Animal ,Hepatitis, Autoimmune ,biology.protein ,Natural Killer T-Cells ,Interleukin-4 ,Antibody ,Mitogens ,CD8 ,Signal Transduction - Abstract
Concanavalin A (Con A)-induced hepatitis is a T-cell-mediated murine experimental model of autoimmune hepatitis. Mice lacking Valpha14 NKT cells were found to be less sensitive to this hepatitis and the MRL/Mp-Fas(lpr/lpr) (MRL/lpr; i.e. Fas deficient) mice were also less sensitive. We report herein that MRL/Mp-Fas(lpr/lpr)-Sap(rpl/-) (MRL/lpr/rpl) mice lack Valpha14 NKT cells and are deficient in the Fas antigen but sensitive to Con A-induced hepatitis. The signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is an adaptor molecule containing a Src homology 2 (SH2) domain. We previously reported new mutant mice found among MRL/lpr mice and revealed that SAP deficiency led to the regression of autoimmune phenotypes in mutant MRL/lpr/rpl mice. It was also revealed that CD4(+) and CD8(+) T cells were effector cells and that blockade of 2B4, one of the SLAM family receptors, inhibited the induction of hepatitis in MRL/lpr/rpl mice. These data suggest that signals mediated by molecules other than SAP from 2B4 in T cells played important roles in the induction of hepatitis in MRL/lpr/rpl mice.
- Published
- 2009