A synthetic mimetic of CD4 is able to suppress disease in a rodent model of immune colitis

Susumu Okamoto, Mamoru Watanabe, Motomi Yamazaki, Tomoharu Yajima, Tatsuhiko Hayashi, Hiromasa Ishii, Makio Mukai, Takaya Yamada, Noriaki Watanabe, Bradford A. Jameson, Toshifumi Hibi

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42 Citations (Scopus)

Abstract

CD4+ mucosal T cells mediate the intestinal inflammation in Crohn's disease and may serve as an important target for immune intervention. Here we assessed the therapeutic effect of a synthetic mimetic of CD4 designed to mimic both the sequence and conformation of the complementarity-determining region 3 of murine CD4 V1 domain (rD-mPGPtide) in a mouse colitis model using immunization with 2,4,6-trinitrobenzene sulfonic acid (TNB). i.v. administration of the rD-mPGPtide but not control scrambled peptide could suppress severe inflammation in the chronic colitis mouse model. After treatment with the rD-mPGPtide, a striking improvement of diarrhea and acute wasting disease was observed with decreased mortality. Serum anti-TNB antibody titers, CD45RB(low)CD4+ T cells in the lamina propria and IFN-γ mRNA expression in the mucosa were significantly decreased with the rD-mPGPtide treatment. Anti-CD4 antibody also suppressed disease by depletion of CD45RB(high)CD4+ T cells in the colonic mucosa. The observation that the synthetically engineered analogue of murine CD4 inhibits inflammation in a rodent disease model by different mechanisms than anti-CD4, antibody suggests that a human version of this peptide has potential therapeutic utility in CD4+ mucosal T cell-mediated intestinal inflammation in Crohn's disease.

Original languageEnglish
Pages (from-to)355-366
Number of pages12
JournalEuropean Journal of Immunology
Volume29
Issue number1
DOIs
Publication statusPublished - 1999

Keywords

  • CD4
  • Crohn's disease
  • Experimental colitis
  • Th1 cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Okamoto, S., Watanabe, M., Yamazaki, M., Yajima, T., Hayashi, T., Ishii, H., Mukai, M., Yamada, T., Watanabe, N., Jameson, B. A., & Hibi, T. (1999). A synthetic mimetic of CD4 is able to suppress disease in a rodent model of immune colitis. European Journal of Immunology, 29(1), 355-366. https://doi.org/10.1002/(SICI)1521-4141(199901)29:01<355::AID-IMMU355>3.0.CO;2-G