Rheumatoid arthritis (RA) is a systemic
autoimmune disease mediated by T cells.
Collagen type II (CII) is one of the
autoantigens associated with RA. CII263-272 is a predominant CII antigenic
peptide that can induce T-cell activation upon binding to MHC and interaction with the appropriate
T-cell receptor (TCR). Altered CII263-272
peptides with substitution of specific
amino acids could bind to RA-associated HLA-DR4/1 with no T cell stimulating effects and could inhibit T cell activation in RA. We performed this study to evaluate the effect of
mucosal administration and to explore the mechanism of the inhibitory effect of altered CII263-272
peptide (267Q-->A, 270K-->A and 271G-->A) on
collagen induced arthritis (CIA). CIA was induced in Lewis rats by immunization with bovine CII. Altered CII263-272
peptide was given intranasally beginning from
arthritis onset. Wild CII263-272
peptide or PBS was administered as controls.
Therapeutic effects were evaluated by
arthritis scores,
body weight change, and joint pathologic scores. The anti-CII antibody and its subtypes and the
cytokines, IFN-gamma,
IL-10, and
IL-17 were measured with ELISA. Foxp3+CD4+CD25+ regulatory T cell induction was assessed by FACS analysis. Following treatment with the altered CII263-272
peptide, arthiritis scores were reduced and
body weight was increased. The altered CII263-272
peptide could retard the histologic lesion of the joints. The titers of anti-CII
antibodies IgG2a in altered CII263-272
peptide treated rats decreased markedly compared to PBS-treated rats. The serum levels of IFN-gamma in rats treated with altered
peptide was lower than that of rats treated with wild CII263-272
peptide and PBS. No differences were observed in the levels of serum
IL-10 among the three groups. The altered CII263-272
peptide could decrease serum level of
IL-17 and increase peripheral Foxp3+CD4+CD25+ T cells at early stage of CIA.
Mucosal administration of altered CII263-272
peptide could effectively inhibit the progression of CIA. Altered CII263-272
peptide could suppress Th17 cells and expand regulatory T cells in the early stage of the disease. The
IgG2a subtype of anti-CII
antibodies and IFN-gamma were reduced and in vivo Th1 responses were inhibited as a result of altered CII
peptide treatment. Altered CII
peptide is likely therapeutic in RA.