Collagen-specific T-cell repertoire in blood and synovial fluid varies with disease activity in early rheumatoid arthritis.
BACKGROUND
Type II collagen is a DR4/DR1 restricted target of self-reactive T cells that sustain rheumatoid arthritis. The aim of the present study was to analyze the T-cell receptor repertoire at the onset of and at different phases in rheumatoid arthritis.


METHODS
We used the CDR3 BV-BJ spectratyping to study the response to human collagen peptide 261-273 in 12 patients with DR4+ rheumatoid arthritis (six at the onset of disease and six during the course of disease) and in five healthy DR4+ relatives.


RESULTS
The collagen-specific T-cell repertoire is quite restricted at the onset of disease, involving approximately 10 rearrangements. Within the studied collagen-specific rearrangements, nearly 75% is shared among patients. Although the size of the repertoire used by control individuals is comparable to that of patients, it is characterized by different T-cell receptors. Part of the antigen-specific T-cell repertoire is spontaneously enriched in synovial fluid. The specific T-cell repertoire in the periphery was modulated by therapy and decreased with the remission of the disease. Failure of immunoscopy to detect this repertoire was not due to suppression of collagen-driven proliferation in vitro by CD4+ CD25+ T cells. Clinical relapse of the disease was associated with the appearance of the original collagen-specific T cells.


CONCLUSIONS
The collagen-specific T-cell receptor repertoire in peripheral blood and synovial fluid is restricted to a limited number of rearrangements in rheumatoid arthritis. The majority of the repertoire is shared between patients with early rheumatoid arthritis and it is modulated by therapy.
Ria
Francesco
F
Institute of General Pathology, Catholic University, Largo F Vito, Rome, Italy. fria@rm.unicatt.it
Penitente
Romina
R
De Santis
Maria
M
Nicolò
Chiara
C
Di Sante
Gabriele
G
Orsini
Massimiliano
M
Arzani
Dario
D
Fattorossi
Andrea
A
Battaglia
Alessandra
A
Ferraccioli
Gian Franco
GF
D000328:Adult; D000368:Aged; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000378:metabolism; D049109:Cell Proliferation; D015331:Cohort Studies; D024043:Collagen Type II / Q000097:blood* / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D005260:Female; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D013582:Synovial Fluid / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
D024043:Collagen Type II; D018984:Epitopes, T-Lymphocyte