TY - JOUR
T1 - MHC class II derived recombinant T cell receptor ligands protect DBA/1LacJ mice from collagen-induced arthritis
AU - Huan, Jianya
AU - Kaler, Laurie J.
AU - Mooney, Jeffery L.
AU - Subramanian, Sandhya
AU - Hopke, Corwyn
AU - Vandenbark, Arthur A.
AU - Rosloniec, Edward F.
AU - Burrows, Gregory G.
AU - Offner, Halina
PY - 2008/1/15
Y1 - 2008/1/15
N2 - We previously demonstrated the therapeutic effects of MHC class II derived recombinant T cell receptor ligands (RTL), singlechain two domain complexes of the α1 and β1 domains of MHC class II molecules genetically linked with an immunodominant peptide, in experimental autoimmune encephalomyelitis. In the current study, we produced a monomeric murine I-Aq-derived RTL construct covalently linked with bovine collagen type II peptide (bCII257-270) suitable for use in DBA/1LacJ mice that develop collagen-induced arthritis (CIA), an animal model of human rheumatoid arthritis, after immunization with bCII protein in CFA. In this study, we demonstrate that the I-A q-derived RTLs reduced the incidence of the disease, suppressed the clinical and histological signs of CIA and induced long-term modulation of T cells specific for arthritogenic Ags. Our results showed that the I-A q/bCII257-270 molecule could systemically reduce proinflammatory IL-17 and IFN-γ production and significantly increase anti-inflammatory IL-10, IL-13, and FoxP3 gene expression in splenocytes. Moreover, I-A q/bCII257-270 molecule could also selectively inhibit IL-1β, IL-6, and IL-23 expression in local joint tissue. This is the first report demonstrating effective prevention of joint inflammation and clinical signs of CIA with an I-Aq-derived RTL, thus supporting the possible clinical use of this approach for treating rheumatoid arthritis in humans.
AB - We previously demonstrated the therapeutic effects of MHC class II derived recombinant T cell receptor ligands (RTL), singlechain two domain complexes of the α1 and β1 domains of MHC class II molecules genetically linked with an immunodominant peptide, in experimental autoimmune encephalomyelitis. In the current study, we produced a monomeric murine I-Aq-derived RTL construct covalently linked with bovine collagen type II peptide (bCII257-270) suitable for use in DBA/1LacJ mice that develop collagen-induced arthritis (CIA), an animal model of human rheumatoid arthritis, after immunization with bCII protein in CFA. In this study, we demonstrate that the I-A q-derived RTLs reduced the incidence of the disease, suppressed the clinical and histological signs of CIA and induced long-term modulation of T cells specific for arthritogenic Ags. Our results showed that the I-A q/bCII257-270 molecule could systemically reduce proinflammatory IL-17 and IFN-γ production and significantly increase anti-inflammatory IL-10, IL-13, and FoxP3 gene expression in splenocytes. Moreover, I-A q/bCII257-270 molecule could also selectively inhibit IL-1β, IL-6, and IL-23 expression in local joint tissue. This is the first report demonstrating effective prevention of joint inflammation and clinical signs of CIA with an I-Aq-derived RTL, thus supporting the possible clinical use of this approach for treating rheumatoid arthritis in humans.
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U2 - 10.4049/jimmunol.180.2.1249
DO - 10.4049/jimmunol.180.2.1249
M3 - Article
C2 - 18178865
AN - SCOPUS:40449142272
SN - 0022-1767
VL - 180
SP - 1249
EP - 1257
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -