Evidence for Preferential T Cell Receptor Vβ Gene Usage and T Cell Clonal Expansion in the Synovium of BB Rats with Early-Onset Collagen-Induced Arthritis

Type II collagen (CII) is a potent arthritogen in the BB rat. To determine whether a restricted group of T cells is involved in the pathogenesis of collagen-induced arthritis, lymphocytes from synovium, peripheral blood, and lymph nodes of arthritic rats were studied for T cell receptor (TCR) Vβ gene usage using polymerase chain reaction (PCR). Oligoclonal TCR Vβ usage was found only insynovium recovered day 2 post-arthritis onset, but not day 7; lymph node and peripheral blood T cells showed diverse TCR usage at both times. To determine whether T cell local clonal expansion occurred in synovium at day 2 of arthritis, cDNAfor four TCR β families was sequenced through VDJ regions. Strong selective expansion of TCR Vβ 8.2,4, and 17 was noted. Importantly, the dominant clonotype of Vβ 8.2 was identical to that of a lymph node-derived T hybridoma specific for the immunodominant epitope in CII(181–210). Cells from synovium (day 2 postonset) analyzed by flow cytometry also showed Vβ 8.2+cell enrichment. These observations, plus finding that T cells from inflamed synovium respond to CII(181–201)in vitro,suggest the local recruitment and clonal expansion of some T cells families, possibly driven by autologous CII released during cartilage degradation.