Role of 2B4-mediated signals in the pathogenesis of a murine hepatitis model independent of Fas and Valpha14 NKT cells.

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.

• Authors: Hiroshi Furukawa, Hiroshi Kitazawa, Izumi Kaneko, Mitsunobu Matsubara, Masato Nose, Masao Ono
• Journal: Immunology (Immunology) Vol. 128 Issue 1 Suppl Pg. e151-8 (Sep 2009) ISSN: 1365-2567 [Electronic] England
• PMID: 18800987 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD
• Cd244a protein, mouse
• Immunologic Factors
• Mitogens
• Receptors, Immunologic
• Signaling Lymphocytic Activation Molecule Family
• fas Receptor
• Concanavalin A
• Interleukin-4

Topics

• Animals
• Antibodies, Monoclonal (immunology)
• Antigens, CD (immunology)
• CD4-Positive T-Lymphocytes (drug effects, immunology)
• CD8-Positive T-Lymphocytes (drug effects, immunology)
• Concanavalin A (administration & dosage, pharmacology)
• Disease Models, Animal
• Hepatitis, Autoimmune (immunology)
• Immunologic Factors (pharmacology)
• Interleukin-4 (immunology, metabolism)
• Mice
• Mice, Inbred MRL lpr
• Mice, Mutant Strains
• Mitogens (administration & dosage, pharmacology)
• Natural Killer T-Cells (immunology)
• Receptors, Immunologic (immunology)
• Signal Transduction (immunology)
• Signaling Lymphocytic Activation Molecule Family
• fas Receptor (genetics, immunology)