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

研究成果: Article査読

43 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)355-366
ページ数12
ジャーナルEuropean Journal of Immunology
29
1
DOI
出版ステータスPublished - 1999

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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