Cellular and Humoral Immune Response Against Articular Chondrocytes and Proteoglycans in Rheumatoid Arthritis

Abstract

The hallmark of many inflammatory and degenerative joint diseases is the destruction of cartilage. Normally, cartilage is an immunologically privileged, sequestered tissue that has been shown to possess tissue-specific matrix and cell surface antigens [1]. These antigens may cause autoimmune reactions when exposed to the immune system during traumatic or inflammatory processes. Moreover, HLA class-II (Ia) antigens have been demonstrated on human articular chondrocytes, which normally do not express these surface molecules, in certain joint diseases including rheumatoid arthritis (Fig. 1) [2, 3]. In vitro, HLA class-II antigens can be induced on constitutively Ia-negative human chondrocytes by γ-interferon [4]. An aberrant HLA class-II antigen expression in affected organs is a general phenomenon in autoimmune diseases such as thyroiditis, juvenile diabetes mellitus, lichen ruber planus, and primary biliary cirrhosis [5–7]. It has been suggested that this expression contributes to the initiation of autoimmune reactions [8]. Rabbit articular chondrocytes have been shown to bear Ia antigens constitutively [9]. In this species, chondrocytes are able to stimulate allogeneic and autologous T lymphocytes [9–11]. Furthermore, rabbit articular chondrocytes have been shown to function as antigen-presenting cells [9].