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

Objective. Male mice of the DBA/1 inbred strain spontaneously develop polya rthritis and toe stiffness when they are greater than or equal to 4 months old. The arthritis affects predominantly the proximal interphalangeal joint s and the ankle of the hind limbs. The current study was aimed at determini ng the importance of T lymphocytes in this disease. Methods. Histologic sections of hindpaws from arthritic DBA/1 mice were exa mined. The role of T lymphocytes was studied by using mice lacking either a lpha/beta or gamma/delta T cells due to a deletion in T cell receptor beta (TCR beta) or TCR delta genes. Results. Arthritis was associated with a massive proliferation of connectiv e tissue (fibroblasts) in synovium and adjacent tissues. Chondroid and bone tissue outgrowth at the entheses generated periarticular osteophytes (enth esophytes) 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 unaffe cted. Abnormal chondroid tissue formation was common in stiffened toes, sug gesting that the same pathology may underlie both joint stiffness and arthr itis. Dividing chondrocytes were commonly seen in tendons, but without corr elation with arthritis or toe stiffness. Mice lacking alpha/beta or gamma/d elta T cells developed arthritis at the same incidence as control littermat es. Conclusion. The naturally occurring arthritis in male DBA/1 mice is a T cel l-independent enthesopathy characterized by periarticular hyperostosis and marginal ankylosis, This suggests that the ossification leading to peripher al ankylosis of the joints in human enthesopathies, such as diffuse idiopat hic skeletal hyperostosis and seronegative spondylarthropathies, is a T cel l-independent process.