Accumulation of multiple T cell clonotypes in the synovial lesions of patients with rheumatoid arthritis revealed by a novel clonality analysis

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Abstract
T cell activation in the characteristic synovial lesions of rheumatoid arthritis may play a major role in the pathogenesis of this autoimmune disease. Analysis of T cell clonal diversity in these sites remains equivocal. Using the PCR and subsequent single-strand conformation polymorphism analysis it is possible to assess the degree of junctional diversity In the TCR with minimal selection bias. Concentrating on the β-chain of the TCR, a paucity of clonotypic T cell expansion is demonstrated in the peripheral blood of healthy Individuals. After polyclonal stimulation in vitro (with concanavalln A or phytohemagglutlnln) this pattern does not change. In contrast, some T cell clonotypes appear following in vitro stimulation with purified protein derivative. Analysis of the peripheral blood, synovial fluid, and synovial tissue of patients with rheumatoid arthritis indicated many dominant T cell clonotypes. These data argue for a clonally diverse T cell response In the affected tissues of rheumatoid arthritic subjects.

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