Tumour necrosis factor receptor gene therapy affects cellular immune responses in collagen induced arthritis in mice

P. Mukherjee, S. Y. Yang, B. Wu, Z. Song, L. K. Myers, P. D. Robbins, P. H. Wooley

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Background: 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 334-300 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.

Original languageEnglish (US)
Pages (from-to)1550-1556
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume64
Issue number11
DOIs
StatePublished - Nov 2005
Externally publishedYes

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