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Role of 2B4‐mediated signals in the pathogenesis of a murine hepatitis model independent of Fas and Vα14 NKT cells
Author(s) -
Furukawa Hiroshi,
Kitazawa Hiroshi,
Kaneko Izumi,
Matsubara Mitsunobu,
Nose Masato,
Ono Masao
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.02936.x
Subject(s) - cd8 , autoimmune hepatitis , hepatitis , immunology , natural killer t cell , biology , antigen , microbiology and biotechnology , chemistry
Summary Concanavalin A (Con A)‐induced hepatitis is a T‐cell‐mediated murine experimental model of autoimmune hepatitis. Mice lacking Vα14 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 Vα14 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.