Abstract
IntroductionType 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.MethodsWe 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.ResultsThe 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.ConclusionsThe 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.
Highlights
Introduction Type II collagen is aDR4/DR1 restricted target of self-reactive T cells that sustain rheumatoid arthritis
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
Summary
DR4/DR1 restricted target of self-reactive T cells that sustain rheumatoid arthritis. There is a general consensus that self-reactive mechanisms are largely responsible for the pathogenesis of RA. The autoantibody response to a highly conserved protein, type II collagen, occurring during the first few years of the disease clearly indicates that self-reactive B cells are present [5,6,7,8,9]. The infiltration of T cells in the synovial tissue and the demonstration that there is autoreactivity of T cells against type II collagen [10,11,12,13] suggest that a cell-mediated immune response plays a prominent role in joint inflammation.
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