Role of 2B4-mediated signals in the pathogenesis of a murine hepatitis model independent of Fas and Vα14 NKT cells

Hiroshi Furukawa, Hiroshi Kitazawa, Izumi Kaneko, Mitsunobu Matsubara, Masato Nose, Masao Ono

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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-Faslpr/lpr-Saprpl/- (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.

Original languageEnglish
Pages (from-to)e151-e158
JournalImmunology
Volume128
Issue number1 PART 2
DOIs
Publication statusPublished - 2009 Sep

Keywords

  • 2B4
  • Concanavalin A-induced hepatitis
  • Fas
  • SAP
  • SLAM family receptors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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