Restricted expression of T cell receptor V beta and lymphokine genes in arthritic joints of a TCR V beta a (H-2q) 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) V beta genes in T cells isolated from the inflamed joints, draining lymph nodes and the spleens of BUB/BnJ (H-2q) 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 V beta s, in arthritic joints of mice, during the early phase of the disease was limited to TCR V beta 3 and 10 gene families. In contrast, TCR V beta 4, 7, and 15 were predominant in the draining lymph nodes (LNs) and TCR V beta 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 V beta a genotype mice use a restricted repertoire of TCR V beta 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-gamma 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.