Hapten-Induced Model of Murine Inflammatory Bowel Disease: Mucosal Immune Responses and Protection by Tolerance

Charles O. Elson, Kenneth W. Beagley, Almaz T. Sharmanov, Kohtaro Fujihashi, Hiroshi Kiyono, Gary S. Tennyson, Yingzi Cong, C. Allen Black, Ben W. Ridwan, Jerry R. McGhee

Research output: Contribution to journalArticle

201 Scopus citations

Abstract

We report here a murine model for experimental chronic colitis where administration of trinitrobenzene sulfonic acid (TNBS) in 50% ethanol induced inflammation of large intestine in susceptible (C3H/HeJ and BALB/c) but not resistant (C57BL/6 and DBA/2) mouse strains. We queried whether mucosal trinitrophenyl (TNP)-specific B cell responses were induced in mice with TNBS-induced colitis, and if induction of tolerance to TNBS by oral administration of this hapten protected mice from development of colitis. Isotypes and subclasses of polyclonal and TNP-specific Ab-forming cells (AFC) were assessed in mucosal and peripheral lymphoid tissues of C3H/HeJ mice with TNBS-induced colitis. Increased numbers of IgA- and IgG-secreting cells were found in the inflamed colon lamina propria. Inflamed colonic tissue also contained high frequencies of IgG anti-TNP AFC (predominantly of IgG1, IgG2a, and IgG2b subclasses); however, anti-TNP responses in noninflammed mucosal tissues of mice with colitis exhibited dominant IgA and IgM with low IgG anti-TNP responses. CD4+ T cells stimulated with TNP-splenocytes produced more IFN- γ and less IL-4, suggesting a Th1-type response. Oral administration of TNBS before induction of colitis markedly decreased mucosal anti-TNP responses and completely inhibited anti-TNP IgG2a and IgG2b responses. Control mice did not show inhibition of anti-TNP AFC responses or TNBS-induced colitis. Intracolonic sensitization of susceptible C3H/HeJ mice with TNBS induces a localized IgG anti-TNP B cell response in the inflamed tissue, whereas prior oral administration of TNBS results in unresponsiveness to this agent and protects mice from development of TNBS-induced colitis.

Original languageEnglish (US)
Pages (from-to)2174-2185
Number of pages12
JournalJournal of Immunology
Volume157
Issue number5
StatePublished - Sep 1 1996

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Elson, C. O., Beagley, K. W., Sharmanov, A. T., Fujihashi, K., Kiyono, H., Tennyson, G. S., Cong, Y., Allen Black, C., Ridwan, B. W., & McGhee, J. R. (1996). Hapten-Induced Model of Murine Inflammatory Bowel Disease: Mucosal Immune Responses and Protection by Tolerance. Journal of Immunology, 157(5), 2174-2185.