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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-1-26
pubmed:abstractText
Immunotherapy of rheumatoid arthritis (RA) using oral-dosed native chicken or bovine type II collagen (nCII) to induce specific immune tolerance is an attractive strategy. However, the majority of clinical trials of oral tolerance in human diseases including RA in recent years have been disappointing. Here, we describe a novel recombinant peptide rcCTE1-2 which contains only two tolerogenic epitopes (CTE1 and CTE2) of chicken type II collagen (cCII). These are the critical T-cell determinants for suppression of RA that were first developed and used to compare its suppressive effects with ncCII on the collagen-induced arthritis (CIA) model. The rcCTE1-2 was produced using the prokaryotic pET expression system and purified by Ni-NTA His affinity chromatography. Strikingly, our results showed clearly that rcCTE1-2 was as efficacious as ncCII at the dose of 50 microg/kg/d. This dose significantly reduced footpad swelling, arthritic incidence and scores, and deferred the onset of disease. Furthermore, rcCTE1-2 of 50 microg/kg/d could lower the level of anti-nCII antibody in the serum of CIA animals, decrease Th1-cytokine INF-gamma level, and increase Th3-cytokine TGF-beta(1) produced level by spleen cells from CIA mice after in vivo stimulation with ncCII. Importantly, rcCTE1-2 was even more potent than native cCII, which was used in the clinic for RA. Equally importantly, the findings that the major T-cell determinants of cCII that are also recognized by H-2(b) MHC-restricted T cells have not previously been reported. Taken together, these results suggest that we have successfully developed a novel recombinant peptide rcCTE1-2 that can induce a potent tolerogenic response in CIA.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0161-5890
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
729-37
pubmed:meshHeading
pubmed-meshheading:19041137-Animals, pubmed-meshheading:19041137-Antibodies, pubmed-meshheading:19041137-Arthritis, Experimental, pubmed-meshheading:19041137-Chickens, pubmed-meshheading:19041137-Collagen Type II, pubmed-meshheading:19041137-Desensitization, Immunologic, pubmed-meshheading:19041137-Epitopes, pubmed-meshheading:19041137-Epitopes, T-Lymphocyte, pubmed-meshheading:19041137-Female, pubmed-meshheading:19041137-Immune Tolerance, pubmed-meshheading:19041137-Immunotherapy, pubmed-meshheading:19041137-Interferon-gamma, pubmed-meshheading:19041137-Mice, pubmed-meshheading:19041137-Mice, Inbred Strains, pubmed-meshheading:19041137-Peptides, pubmed-meshheading:19041137-Recombinant Proteins, pubmed-meshheading:19041137-T-Lymphocytes, pubmed-meshheading:19041137-Transforming Growth Factor beta
pubmed:year
2009
pubmed:articleTitle
A novel recombinant peptide containing only two T-cell tolerance epitopes of chicken type II collagen that suppresses collagen-induced arthritis.
pubmed:affiliation
Department of Immunology and National Center for Biomedicine Analysis, Beijing 307 Hospital Affiliated to Academy of Medical Sciences, No. 8, Dongda Ave, Fengtai District, Beijing 100071, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't