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A synthetic mimetic of CD4 is able to suppress disease in a rodent model of immune colitis
Journal article   Open access   Peer reviewed

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, …
European journal of immunology, v 29(1), pp 355-366
Jan 1999
DOI: https://doi.org/10.1002/(SICI)1521-4141(199901)29:01<355::AID-IMMU355>3.0.CO;2-G
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1002/(sici)1521-4141(199901)29:01<355::aid-immu355>3.0.co;2-gView
Published, Version of Record (VoR) Open Maybe Open Access (Publisher Bronze)
url
https://doi.org/10.1002/(SICI)1521-4141(199901)29:01<355::AID-IMMU355>3.0.CO;2-GView
Published, Version of Record (VoR) Open

Abstract

CD4 Crohn's disease Experimental colitis Th1 cell
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, CD45RBlowCD4+ 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 CD45RBhighCD4+ 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.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Immunology
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