Abstract
OBJECTIVE—To investigate whether type II collagen (CII) is recognised by oligoclonally expanded synovial T cells of patients with rheumatoid arthritis (RA). METHODS—Peripheral blood mononuclear cells (PBMC) from 15 RA patients were stimulated with CII in vitro. T cell clones expanded by such stimulation were compared with the clonally expanded synovial T cells by using T cell receptor (TCR) B chain gene specific reverse transcription-polymerase chain reaction and subsequent single strand conformation polymorphism analyses. RESULTS—Stimulation of the heterogeneous peripheral T cells with CII induced clonal expansion of T cells. In three of 15 patients, a proportion of these clones (approximately 17% to 25%) was found to be identical to expanded T cell clones in the synovium in vivo. CONCLUSION—T cell clones that had TCR CDR3 sequences identical to those induced by purified CII were found in a proportion of RA patients. This finding suggests that CII is recognised by T cells that accumulate clonally in RA joints. Oligoclonal T cell expansion in RA joints is probably driven, at least in part, by intra-articular components such as CII.
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Figure 1 .
Comparison of T cell clonotypes between CII stimulated peripheral T cells and in vivo synovial T cells by RT-PCR-SSCP. TCR BV gene products were electrophoresed on the same SSCP gels. (A) BV13S1 from patient 1; (B), BV12 from patient 1; (C), BV1 from patient 2, (D), BV16 from patient 3. P = PBMC cultured with rIL2 alone; B = PBMC cultured with bCII and rIL2; H = PBMC cultured with hCII and rIL2; S = in vivo synovial T cells. Arrows indicate bands with identical migration between hCII stimulated PBMC (lane H) and synovial tissue infiltrating T cells in vivo (lane S).