Accumulation of multiple T cell clonotypes in the synovial lesions of patients with rheumatoid arthritis revealed by a novel clonality analysis.
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 beta-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 concanavalin A or phytohemagglutinin) 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.
Yamamoto
K
K
Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Japan.
Sakoda
H
H
Nakajima
T
T
Kato
T
T
Okubo
M
M
Dohi
M
M
Mizushima
Y
Y
Ito
K
K
Nishioka
K
K
D001172:Arthritis, Rheumatoid / Q000473:pathology*; D001327:Autoimmune Diseases / Q000473:pathology*; D002999:Clone Cells / Q000473:pathology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D008213:Lymphocyte Activation; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013582:Synovial Fluid / Q000166:cytology*; D016176:T-Lymphocyte Subsets / Q000473:pathology*
D016693:Receptors, Antigen, T-Cell, alpha-beta