Restricted Expression of T Cell Receptor Vβ and Lymphokine Genes in Arthritic Joints of a TCR Vβ^A (H-2^Q) Mouse Strain-BUB/BnJ-with Collagen-Induced Arthritis

Abstract

Type II collagen-induced arthritis (CIA) is an animal model of inflammatory polyarthritis with clinical and pathological features resembling rheumatoid arthritis (RA). We compared the expression of T cell receptor (TCR) Vβ genes in T cells isolated from the inflamed joints, draining lymph nodes and the spleens of BUB/BnJ (H-2^q) mice (BUB) during the early phase of CIA. We also investigated the profiles of cytokine gene expression in T cells obtained from the same tissues. We found that the expression of TCR Vβs, in arthritic joints of mice, during the early phase of the disease was limited to TCR Vβ 3 and 10 gene families. In contrast, TCR Vβ 4, 7, and 15 were predominant in the draining lymph nodes (LNs) and TCR Vβ 2, 6, and 14 were predominant in the spleens of arthritic mice. Molecular cloning and sequence analysis revealed that the T cell populations in the arthritic joints were oligoclonal as determined by the limited N-D-N region diversity observed in the sequenced clones. These results demonstrate, for the first time, that (1) joint infiltrating T cells in TCR Vβ^a genotype mice use a restricted repertoire of TCR Vβ genes; (2) there was oligoclonal expansion of infiltrating T cells in arthritic joints in mice with collagen-induced arthritis. Our results on cytokine gene expression in the arthritic joints of BUB mice indicate that Th-1-like T cell derived cytokines may be the predominant cytokines in the arthritic joints as illustrated by the presence of transcripts for IL-2 and IFN-γ but not IL-4. In summary, our results provide evidence that T cells with restricted specificities, and more specificially, Th-1 type T cells, are crucial in the early phase of collagen induced arthritis in mice.

Key Words:

• TCR
• arthritis
• PCR