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Research Article Free access | 10.1172/JCI117561

Dominant clonotypes in the repertoire of peripheral CD4+ T cells in rheumatoid arthritis.

J J Goronzy, P Bartz-Bazzanella, W Hu, M C Jendro, D R Walser-Kuntz, and C M Weyand

Division of Rheumatology, Mayo Clinic, Rochester, Minnesota 55905.

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Published November 1, 1994 - More info

Published in Volume 94, Issue 5 on November 1, 1994
J Clin Invest. 1994;94(5):2068–2076. https://doi.org/10.1172/JCI117561.
© 1994 The American Society for Clinical Investigation
Published November 1, 1994 - Version history
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Abstract

Clonal expansion of T cell specificities in the synovial fluid of patients has been taken as evidence for a local stimulation of T cells. By studying the T cell receptor (TCR) repertoire of CD4+ T cells in the synovial and peripheral blood compartments of patients with early rheumatoid arthritis (RA), we have identified clonally expanded CD4+ populations. Expanded clonotypes were present in the peripheral blood and the synovial fluid but were not preferentially accumulated in the joint. Dominant single clonotypes could not be isolated from CD4+ cells of HLA-DRB1*04+ normal individuals. Clonal expansion involved several distinct clonotypes with a preference for V beta 3+, V beta 14+, and V beta 17+CD4+ T cells. A fraction of clonally related T cells expressed IL-2 receptors, indicating recent activation. The frequencies of clonally expanded V beta 17+CD4+ T cells fluctuated widely over a period of one year. Independent variations in the frequencies of two distinct clonotypes in the same patient indicated that different mechanisms, and not stimulation by a single arthritogenic antigen, were involved in clonal proliferation. These data support the concept that RA patients have a grossly imbalanced TCR repertoire. Clonal expansion may result from intrinsic defects in T cell generation and regulation. The dominance of expanded clonotypes in the periphery emphasizes the systemic nature of RA and suggests that T cell proliferation occurs outside of the joint.

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