Hapten-induced model of murine inflammatory bowel disease: mucosa immune responses and protection by tolerance

J Immunol. 1996 Sep 1;157(5):2174-85.

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 noninflamed 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-gamma 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Administration, Rectal
  • Animals
  • Antibody Formation
  • CD4-Positive T-Lymphocytes / metabolism
  • Cytokines / biosynthesis
  • Disease Models, Animal
  • Epitopes / immunology
  • Female
  • Haptens / administration & dosage
  • Haptens / immunology*
  • Immune Tolerance*
  • Immunosuppressive Agents / toxicity
  • Inflammatory Bowel Diseases / etiology*
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / prevention & control*
  • Intestinal Mucosa / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Trinitrobenzenes / immunology
  • Trinitrobenzenesulfonic Acid / administration & dosage
  • Trinitrobenzenesulfonic Acid / immunology

Substances

  • Cytokines
  • Epitopes
  • Haptens
  • Immunosuppressive Agents
  • Trinitrobenzenes
  • Trinitrobenzenesulfonic Acid