T Cell Receptor (VR) Bias in the Response of Rheumatoid Arthritis Synovial Fluid T Cells to Connective Tissue Antigens

Abstract

T cell receptor (VB) use in the response to type II collagen and cartilage proteoglycans was analysed in peripheral blood and synovial fluid T cells from RA patients. T cells from RA patients with an immune response to connective tissue antigens, and paired PB and SF samples were stimulated in vitro with type II collagen, high density aggrecan proteoglycans (PG), and the Tcell mitogen concanavalin A. After short term culture, mRNA was extracted from cells and a reverse transcription-polymerase chain reaction was performed, using primers specific for eight TCR VB determinants. Blood cells stimulated with ConA generated strong bands with virtually all the V&bT primers tested, but the TCR (V&bT) expression by SF T cells stimulated with mitogen was biased, suggesting a selection process during joint infiltration. The VB phenotypes of cells responding to PG was restricted in individual RA patients, but the pattern of V&bT use in the the RA population was not consistent. In contrast, the V&bT phenotypes of SF cells responding to CII was highly biased in both individual patients and the RA population, with V&bT14, V&bT17, and V&bT8 phenotypes predominant. We conclude that the Tcell response to connective tissue antigens is restricted compared with mitogen stimulation, with the highest degree of TCR bias seen in the response of SF T cells to stimulation with type II collagen.