T cell–chondrocyte interaction in the pathogenesis of osteoarthritis

Objectives

Several lines of evidence have recently suggested that some immune responses are involved in the pathogenesis of osteoarthritis (OA). Aside from humoral immunity, T cells seem relevant to the development of OA. Previously, we showed that T cells responded to autologous chondrocytes only in OA, suggesting involvement in some role in the pathogenesis of OA. In this study, we investigated the response of chondrocytes contacting with autologous T cells.

Methods

Human chondrocytes are obtained during arthroplasty for OA and fracture. The latter samples served as normals. Enzymatically isolated chondrocytes were cultivated and used within the seconnd passage for the following experiments. Both cells were cultured together with or without separate wells and the production of matrix metalloproteinases (MMPs) and RANTES were measured using ELISA kits. The contact responses were blocked by antibodies for adhesion molecules (LFA-4 and VLA-4).

Results

MMP-1, MMP-3, and MMP-13 were expressed only in chondrocytes. The production of all MMPs was enhanced by contact coculture of chondrocytes with autologous T cells, whereas the production was not enhanced by separate coculture. Blockade of adhesion molecules had no influence on these responses. RANTES was expressed both in T cells and chondrocytes without stimulation. RANTES production was enhanced both in contact and in separate conditions only in OA samples, not in normal samples.

Conclusions

The augmentation of MMP production required T cell–chondrocyte contact mediated by mechanisms different from the adhesion molecules tested. As chondrocytes are surrounded by plenty of extracellular matrix, its contact with other types of cells is extremely rare; however, the chance of contact will appear with the degradation of cartilage. Thus, T-cell-mediated development of OA is supposed possible.