CD45RC(high)CD4+ intestinal mucosal lymphocytes infiltrating in the inflamed colonic mucosa of a novel rat colitis model induced by TNB immunization

Mamoru Watanabe, Yasuo Hosoda, Susumu Okamoto, Motomi Yamazaki, Nagamu Inoue, Yoshitaka Ueno, Yasushi Iwao, Hiromasa Ishii, Noriaki Watanabe, Yoshiki Hamada, Takaya Yamada, Tatsuo Suzuki, Toshifumi Hibi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 of serum 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 CD45RC(high)CD4+ 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, CD45RC(high)CD4+ T cells in the lamina propria and interferon-γ 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.

Original languageEnglish
Pages (from-to)46-55
Number of pages10
JournalClinical Immunology and Immunopathology
Volume88
Issue number1
DOIs
Publication statusPublished - 1998 Jul

Keywords

  • Animal model
  • CD4
  • Crohn's disease
  • Th1
  • Trinitrobenzenesulfonic acid

ASJC Scopus subject areas

  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology

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    Watanabe, M., Hosoda, Y., Okamoto, S., Yamazaki, M., Inoue, N., Ueno, Y., Iwao, Y., Ishii, H., Watanabe, N., Hamada, Y., Yamada, T., Suzuki, T., & Hibi, T. (1998). CD45RC(high)CD4+ intestinal mucosal lymphocytes infiltrating in the inflamed colonic mucosa of a novel rat colitis model induced by TNB immunization. Clinical Immunology and Immunopathology, 88(1), 46-55. https://doi.org/10.1006/clin.1997.4508