CD45RChighCD4+ intestinal mucosal lymphocytes infiltrating in the inflamed colonic mucosa of a novel rat colitis model induced by TNB immunization

Clin Immunol Immunopathol. 1998 Jul;88(1):46-55. doi: 10.1006/clin.1997.4508.


To clarify the role of CD4(+) intestinal mucosal lymphocytes in chronic intestinal inflammation, we developed a new rat colitis model by immunization with 2,4,6-trinitrobenzenesulfonic acid (TNB) in an emulsion with an adjuvant followed by transrectal administration of a low dose of TNB. Moreover, we assessed the therapeutic effect of anti-CD4 monoclonal antibody (mAb) on this model. In concert with the development ofserum anti-TNB Abs, transmural and segmental colitis that mimics some characteristics of human Crohn's disease was induced in the immunized rats. Immunohistochemical analysis showed the increase of infiltrating lamina propria CD4(+) T cells. Flow-cytometric analysis of isolated cells from inflamed mucosa revealed that CD45RChighCD4(+) T cells were significantly increased. Interestingly, intraperitoneal administration of anti-CD4 mAbs could suppress severe inflammation in the model with decrease of anti-TNB Ab titer. After the treatment with anti-CD4 mAbs, CD45RChighCD4(+) T cells in the lamina propria and interferon-gamma mRNA expression in the colonic lamina propria CD4(+) T cells were decreased. These results indicated that Th1 CD4(+) intestinal mucosal T cells have a role in the progress of inflamed lesions in chronic enteritis. They implicate that a therapy targeting mucosal T cells expressing CD4 may be feasible in the treatment of human Crohn's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Base Sequence
  • CD4 Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • Colitis / etiology
  • Colitis / immunology*
  • Colitis / pathology
  • Colon / immunology
  • Colon / pathology
  • Crohn Disease / therapy
  • Cytokines / genetics
  • DNA Primers / genetics
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Humans
  • Immunization
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology
  • Leukocyte Common Antigens / metabolism*
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • Rats
  • Rats, Wistar
  • Trinitrobenzenesulfonic Acid / immunology


  • Antibodies, Monoclonal
  • CD4 Antigens
  • Cytokines
  • DNA Primers
  • RNA, Messenger
  • Trinitrobenzenesulfonic Acid
  • Leukocyte Common Antigens