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 language | English |
|---|---|
| Pages (from-to) | 355-366 |
| Number of pages | 12 |
| Journal | European Journal of Immunology |
| Volume | 29 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1999 |
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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 journal › Article
}
TY - JOUR
T1 - A synthetic mimetic of CD4 is able to suppress disease in a rodent model of immune colitis
AU - Okamoto, Susumu
AU - Watanabe, Mamoru
AU - Yamazaki, Motomi
AU - Yajima, Tomoharu
AU - Hayashi, Tatsuhiko
AU - Ishii, Hiromasa
AU - Mukai, Makio
AU - Yamada, Takaya
AU - Watanabe, Noriaki
AU - Jameson, Bradford A.
AU - Hibi, Toshifumi
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - CD4
KW - Crohn's disease
KW - Experimental colitis
KW - Th1 cell
UR - http://www.scopus.com/inward/record.url?scp=0032921746&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032921746&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1521-4141(199901)29:01<355::AID-IMMU355>3.0.CO;2-G
DO - 10.1002/(SICI)1521-4141(199901)29:01<355::AID-IMMU355>3.0.CO;2-G
M3 - Article
C2 - 9933118
AN - SCOPUS:0032921746
VL - 29
SP - 355
EP - 366
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 1
ER -