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dc.contributor.authorMukherjee, P.
dc.contributor.authorYang, Shang-You
dc.contributor.authorWu, Bin
dc.contributor.authorSong, Zheng
dc.contributor.authorMyers, L.K.
dc.contributor.authorRobbins, Paul D.
dc.contributor.authorWooley, Paul H.
dc.identifier.citationP Mukherjee, S-Y Yang, B Wu, Z Song, L K Myers, P D Robbins, P H Wooley Ann Rheum Dis 2005;64:11 1550-1556 Published Online First: 28 April 2005 doi:10.1136/ard.2004.025619en_US
dc.identifier.issn0003-4967 (Print)
dc.identifier.issn1468-2060 (Electronic)
dc.descriptionClick on the DOI link to access this articleen_US
dc.description.abstractBackground: Collagen induced arthritis (CIA) is an animal model of rheumatoid arthritis (RA) amenable to immunotherapy directed against tumour necrosis factor α (TNFα). Objective: To evaluate whether local TNF receptor (TNF-R) gene therapy in DBA/1 mice exerts an influence beyond anti-inflammatory effects. Two measures of CIA pathogenesis were investigated—namely, immunity to collagen II (CII) 245–270 peptide (the major immunodominant epitope within bovine CII) and the preferential activation of T cell Vβ8.2 variable region receptors in arthritic DBA/1 mice. Methods: DBA/1 mice received single periarticular injections of media or retroviral vectors containing LacZ or human TNF-R into affected arthritic paws at disease onset. Disease severity was monitored, immune responses towards the immunodominant bovine CII 245–270 and subdominant CII 334–360 peptide epitopes were assessed by ELISA, and T cell Vβ usage was analysed by real time polymerase chain reaction for the LacZ transduced, TNF-R, and viral-free media treated control animals. The therapeutic influence of TNF-R gene transduction was compared with other groups at different times after treatment. Results: Reduced disease severity was seen 15–35 days after treatment, with a concomitant increase in immunity towards the subdominant CII 334–360 peptide epitope rather than the immunodominant CII 245–270 peptide in TNF-R treated animals. Early in the disease, TNF-R treated animals demonstrated a reduction of bias towards the otherwise predominant Vβ8.2 T cell subset. Conclusions: TNF-R gene therapy influences cellular immunity in CIA, leading to overall disease amelioration, thus suggesting that TNF inhibition may have therapeutic potential beyond the control of inflammation in RA.en_US
dc.publisherBMJ Publishing Groupen_US
dc.relation.ispartofseriesAnnals of the Rheumatic Diseases;
dc.relation.ispartofseries;V.64, No.11
dc.titleTumour necrosis factor receptor gene therapy affects cellular immune responses in collagen induced arthritis in miceen_US

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