Class II histocompatibility antigen-mediated immunologic function of normal articular chondrocytes

Abstract

Using monoclonal antibodies, we examined the display of rabbit Ia by articular chondrocytes. We found that 29 to 46% of chondrocytes displayed Ia antigen compared with 46 to 60% of spleen cells. Ia antigen expression was not likely to be the result of enzyme treatment. To investigate antigen presenting activity of enzyme dissociated normal articular chondrocytes, adult rabbits were immunized in the front foot pads with ovalbumin (OVA) in complete Freund's adjuvant. Four to six weeks later, draining popliteal lymph node cells (LNC) were obtained. Articular chondrocytes were obtained by overnight collagenase, DNase, and hyaluronidase digestion of cartilage from both ends of femurs and proximal end of tibias. Antigen-presenting cells from spleen were used as positive controls. LNC and nylon wool-purified T cells were cultured with OVA pulsed and mitomycin C-treated chondrocytes or spleen cells, and lymphocyte proliferation was measured by 3H-TdR uptake. Both chondrocytes and spleen cells showed antigen presenting activity, and stimulation of lymphocyte proliferation was inhibited by murine monoclonal anti-rabbit Ia antibody (2C4), whereas control plasmacytoma cell supernatants had no effect. When T cells were purified first by Sephadex G-10 and later by nylon wool columns, these cells were dependent on antigen-presenting cells for immunogen (OVA)-induced lymphocyte proliferation. Again, chondrocytes under these strict experimental conditions presented antigen to T cells. Chondrocytes also stimulated autologous and allogeneic normal lymphocytes. Thus, normal chondrocytes have Ia antigens on their surface and can function as antigen-presenting cells. These results are significant for the understanding of local cellular interaction in the pathogenesis of rheumatoid arthritis.