Inducing experimental arthritis and breaking self tolerance to joint-specific antigens with trackable, OVA-specific T cells

Garside, Paul and Maffia, Pasquale and Brewer, James M. and Gracie, J.A. and Ianaro, Angela and Leung, Bernard P. and Mitchell, Paul J. and Smith, Karen M. and McInnes, Iain B. (2004) Inducing experimental arthritis and breaking self tolerance to joint-specific antigens with trackable, OVA-specific T cells. Journal of Immunology, 173 (1). pp. 151-156. ISSN 0022-1767

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Abstract

The importance of T cell Ag specificity and Th1 vs Th2 phenotype in synovial inflammation remains controversial. Using OVA-specific TCR transgenic T cells from DO11.10 mice, we demonstrate that mice receiving Th1, but not Th2, cells display a transient arthritis following immunization that is characterized by synovial hyperplasia, cellular infiltration, and cartilage erosion. OVA-specific T cells also accumulated in inflamed joints, suggesting that they could exert their inflammatory effect locally in the joint or in the draining lymph node. Importantly, this pathology was accompanied by a breakdown in self-tolerance, as evidenced by the induction of collagen-specific T and B cell responses. This model directly demonstrates a pivotal role for Th1 cells of an irrelevant specificity in the development of inflammatory arthritis. Furthermore, the ability to track these cells in vivo will make feasible studies revealing the dynamic role of T cells in arthritis.

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