Evidence for preferential T cell receptor V beta 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) V beta gene usage using polymerase chain reaction (PCR). Oligoclonal TCR V beta usage was found only in synovium 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, cDNA for four TCR beta families was sequenced through VDJ regions. Strong selective expansion of TCR V beta 8.2, 4, and 17 was noted. Importantly, the dominant clonotype of V beta 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 V beta 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.
Ye
X J
XJ
Department of Medicine, University of Tennessee, Memphis, USA.
Aelion
J
J
Endres
R O
RO
Kang
A H
AH
Cremer
M A
MA
D000595:Amino Acid Sequence; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000209:etiology / Q000276:immunology*; D001483:Base Sequence; D003001:Cloning, Molecular; D003094:Collagen / Q000276:immunology*; D005260:Female; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D051381:Rats; D011913:Rats, Inbred BB; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D003094:Collagen