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The Journal of Immunology, 2004, 173: 151-156.
Copyright © 2004 by The American Association of Immunologists

Inducing Experimental Arthritis and Breaking Self-Tolerance to Joint-Specific Antigens with Trackable, Ovalbumin-Specific T Cells1

Pasquale Maffia*,{ddagger}, James M. Brewer*, J. Alastair Gracie{dagger}, Angela Ianaro{ddagger}, Bernard P. Leung*, Paul J. Mitchell*, Karen M. Smith*, Iain B. McInnes{dagger} and Paul Garside2,*

* Division of Immunology, Infection, and Inflammation, University of Glasgow, Western Infirmary, Glasgow, United Kingdom; {dagger} Centre for Rheumatic Diseases, Division of Immunology, Infection and Inflammation, Glasgow Royal Infirmary, Glasgow, United Kingdom; and {ddagger} Department of Experimental Pharmacology, University of Naples, Napoli, Italy

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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