Role of 2B4-mediated signals in the pathogenesis of a murine hepatitis model independent of Fas and Valpha14 NKT cells.
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.
Furukawa
Hiroshi
H
Department of Pathology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan. hfurukawa@mail.tains.tohoku.ac.jp
Kitazawa
Hiroshi
H
Kaneko
Izumi
I
Matsubara
Mitsunobu
M
Nose
Masato
M
Ono
Masao
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003208:Concanavalin A / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D019693:Hepatitis, Autoimmune / Q000276:immunology*; D007155:Immunologic Factors / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008817:Mice, Mutant Strains; D008934:Mitogens / Q000008:administration & dosage / Q000494:pharmacology; D055611:Natural Killer T-Cells / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D000071176:Signaling Lymphocytic Activation Molecule Family; D019014:fas Receptor / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C490007:Cd244a protein, mouse; D007155:Immunologic Factors; D008934:Mitogens; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D019014:fas Receptor; D003208:Concanavalin A; D015847:Interleukin-4
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