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

Research output: Contribution to journalArticle

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

Fingerprint

Colitis
Rodentia
Inflammation
T-Lymphocytes
Anti-Idiotypic Antibodies
Mucous Membrane
Crohn Disease
Rodent Diseases
Wasting Syndrome
Complementarity Determining Regions
Peptides
Sulfonic Acids
Acute Disease
Therapeutic Uses
Diarrhea
Immunization
Therapeutics
Messenger RNA
Mortality
reverse D amino acid mouse proline-glycine-proline peptide

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

A synthetic mimetic of CD4 is able to suppress disease in a rodent model of immune colitis. / Okamoto, Susumu; Watanabe, Mamoru; Yamazaki, Motomi; Yajima, Tomoharu; Hayashi, Tatsuhiko; Ishii, Hiromasa; Mukai, Makio; Yamada, Takaya; Watanabe, Noriaki; Jameson, Bradford A.; Hibi, Toshifumi.

In: European Journal of Immunology, Vol. 29, No. 1, 1999, p. 355-366.

Research output: Contribution to journalArticle

Okamoto, S, Watanabe, M, Yamazaki, M, Yajima, T, Hayashi, T, Ishii, H, Mukai, M, Yamada, T, Watanabe, N, Jameson, BA & Hibi, T 1999, 'A synthetic mimetic of CD4 is able to suppress disease in a rodent model of immune colitis', European Journal of Immunology, vol. 29, no. 1, pp. 355-366. https://doi.org/10.1002/(SICI)1521-4141(199901)29:01<355::AID-IMMU355>3.0.CO;2-G
Okamoto, Susumu ; Watanabe, Mamoru ; Yamazaki, Motomi ; Yajima, Tomoharu ; Hayashi, Tatsuhiko ; Ishii, Hiromasa ; Mukai, Makio ; Yamada, Takaya ; Watanabe, Noriaki ; Jameson, Bradford A. ; Hibi, Toshifumi. / A synthetic mimetic of CD4 is able to suppress disease in a rodent model of immune colitis. In: European Journal of Immunology. 1999 ; Vol. 29, No. 1. pp. 355-366.
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