| Autor: |
Okamoto S; Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan., Watanabe M, Yamazaki M, Yajima T, Hayashi T, Ishii H, Mukai M, Yamada T, Watanabe N, Jameson BA, Hibi T |
| Jazyk: |
angličtina |
| Zdroj: |
European journal of immunology [Eur J Immunol] 1999 Jan; Vol. 29 (1), pp. 355-66. |
| DOI: |
10.1002/(SICI)1521-4141(199901)29:01<355::AID-IMMU355>3.0.CO;2-G |
| Abstrakt: |
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-gamma 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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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