T lymphocytes are not required for the spontaneous development of entheseal ossification leading to marginal ankylosis in the DBA/1 mouse

Abstract

OBJECTIVE: Male mice of the DBA/1 inbred strain spontaneously develop polyarthritis and toe stiffness when they are > or =4 months old. The arthritis affects predominantly the proximal interphalangeal joints and the ankle of the hind limbs. The current study was aimed at determining the importance of T lymphocytes in this disease. METHODS: Histologic sections of hindpaws from arthritic DBA/1 mice were examined. The role of T lymphocytes was studied by using mice lacking either alpha/beta or gamma/delta T cells due to a deletion in T cell receptor beta (TCRbeta) or TCRdelta genes. RESULTS: Arthritis was associated with a massive proliferation of connective tissue (fibroblasts) in synovium and adjacent tissues. Chondroid and bone tissue outgrowth at the entheses generated periarticular osteophytes (enthesophytes) which were deposited on the unchanged margins of the preexisting bone. In some cases, the enthesophytes enlarged enough to bridge and fuse the bones by marginal ankylosis. Articular cartilage was essentially unaffected. Abnormal chondroid tissue formation was common in stiffened toes, suggesting that the same pathology may underlie both joint stiffness and arthritis. Dividing chondrocytes were commonly seen in tendons, but without correlation with arthritis or toe stiffness. Mice lacking alpha/beta or gamma/delta T cells developed arthritis at the same incidence as control littermates. CONCLUSION: The naturally occurring arthritis in male DBA/1 mice is a T cell-independent enthesopathy characterized by periarticular hyperostosis and marginal ankylosis. This suggests that the ossification leading to peripheral ankylosis of the joints in human enthesopathies, such as diffuse idiopathic skeletal hyperostosis and seronegative spondylarthropathies, is a T cell-independent process.