Limited heterogeneity of rearranged T cell receptor V alpha and V beta transcripts in synovial fluid T cells in early stages of rheumatoid arthritis.
OBJECTIVE
The identification of activated T cells in synovial fluid and synovium, and the association of rheumatoid arthritis (RA) with specific HLA-DR restriction elements, strongly suggest that these T cells play a critical role in the etiology and pathogenesis of RA. Analysis of the T cell receptor (TCR) repertoire in the early stages of RA might be an approach to identify those T cells involved in the initiation and/or perpetuation of the disease.


METHODS
TCR V alpha and V beta transcripts of synovial T cells, sampled at the early stages of RA, were amplified by reverse transcriptase-polymerase chain reaction. HLA-DR subtyping was determined by serologic analysis and dot-blot hybridization of polymerase chain reaction amplification products using digoxigenin-labeled, sequence-specific oligonucleotide probes.


RESULTS
Our findings showed a limited heterogeneity of V alpha and V beta TCRs in synovial fluid T cells, and a preferential usage of TCR V alpha 17 in early RA. In contrast, in the later stages of RA, a more polyclonal TCR V alpha and V beta gene usage was observed.


CONCLUSIONS
Our results support the view that induction of RA is driven by an oligoclonal immune response to an unknown antigen. These findings also suggest a pathogenetic role for V alpha 17 T cells in the early stages of RA.
Fischer
D C
DC
University of Technology Aachen, Germany.
Opalka
B
B
Hoffmann
A
A
Mayr
W
W
Haubeck
H D
HD
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001483:Base Sequence; D005260:Female; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / Q000235:genetics* / Q000276:immunology*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000235:genetics* / Q000276:immunology*; D018740:Genetic Heterogeneity; D006684:HLA-DR Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics / Q000276:immunology
D006684:HLA-DR Antigens; D011948:Receptors, Antigen, T-Cell