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T cell responses to human type II collagen in patients with rheumatoid arthritis and healthy controls
Authors:Neil Snowden MRCP  Irena Reynolds MSc  Keith Morgan  Lennox Holt
Affiliation:1. Lennox Holt, FRCP: University of Manchester, Manchester, UK;2. University of Manchester, Manchester, UK, and Hope Hospital, Salford, UK

Dr. Morgan is deceased.;3. University of Manchester, Manchester, UK, and Hope Hospital, Salford, UK

Abstract:
Objective. To study the prevalence of T cell responses to human type II collagen (CII) in patients with rheumatoid arthritis (RA) with or without antibodies to CII, and in healthy controls. Methods. Assays were performed to study T cell proliferative responses to CII in peripheral blood from 69 patients with RA (11 with anti-CII antibodies and 58 without) and 28 healthy controls. Further analysis was made of the time course of the response and the epitopic specificity, using peptides derived from the cyanogen bromide 11 (CB11) fragment of CII. Results. Significant proliferative responses to CII were found in 50% of patients with anti-CII, 5.3% of RA patients without these antibodies, and 35.7% of healthy controls. Responses in RA patients differed from those in healthy controls; the former had kinetics suggestive of a recall response and the latter that of a primary response. Some common epitopes within CB11 were recognized by T cells from patients and controls. Conclusion. Proliferative T cell responses to CII occur in some healthy individuals, suggesting that thymic tolerance for this antigen may be incomplete. Most patients with RA have no evidence of a T cell response to CII, possibly indicating the development of peripheral tolerance to this antigen as a consequence of cartilage breakdown. However, in a minority of patients, T and B cell responses to CII persist, and may contribute to joint damage.
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