[Pathological study of arthritis induced by type 2 bovine collagen and freund's complete adjuvant in rat]

Because of the pathological similarities between collagen induced arthritis [CIA] and rheumatoid arthritis, the CIA model has been the subject of extensive investigations. This study initiated to evaluate the pathologic lesions of induced arthritis by collagen in a total of 50 female rats [Rattus norvegicus.]. Arthritis was induced by two intrademial injections [14 days interval] of type 2 bovine collagen solution and Freund's complete adjuvant [FCA] into the tail and right leg paw of 40 rats. Severity of arthritis in affected leg was represented in grade to 4. Three weeks after beginning of the experiment, 22, 12, 5 and 1 affected rats were clinically diagnosed with 1, 2, 3 and 4 grades of arthritis respectively. Rats were intradermally injected into the tail showed only slight and moderate [grade 1 and 2] arthritis. Macroscopically, the involved joints were enlarged, swollen and stiff and deformity and ankylosis of affected joints were noticed in severe cases. Deep healing ulcers in planter of the paw were diagnosed in 14 rats. Histopathologic examinations revealed infiltration of mononuclear inflammatory cells and papillary hyperplasia of synovial membrane in mid and moderately affected animals [grade 1 and 2] and erosion of articular cartilage with formation of fibrovascular pannus on its surface in synovial membrane in severe cases [grade 3]. In very severe cases [grade 4], complete destruction of articular cartilage and access of granulation tissue to subchondral bone were noticed. Pathologic lesions of the involved joints were very similar to those reported from rheumatoid arthritis in human, erosive polyarthritis in dog and caprine arthritis/encephalitis

TGF-beta-treated antigen presenting cells suppress collagen-induced arthritis through the promotion of Th2 responses

Collagen-induced arthritis (CIA) is mediated by self-reactive CD4+ T cells that produce inflammatory cytokines. TGF-beta2-treated tolerogenic antigen-presenting cells (Tol-APCs) are known to induce tolerance in various autoimmune diseases. In this study, we investigated whether collagen-specific Tol-APCs could induce suppression of CIA. We observed that Tol-APCs could suppress the development and severity of CIA and delay the onset of CIA. Treatment of Tol-APCs reduced the number of IFN-gamma- and IL-17-producing CD4+ T cells and increased IL-4- and IL-5-producing CD4+ T cells upon collagen antigen stimulation in vitro. The suppression of CIA conferred by Tol-APCs correlated with their ability to selectively induce IL-10 production. We also observed that treatment of Tol-APCs inhibited not only cellular immune responses but also humoral immune responses in the process of CIA. Our results suggest that in vitro-generated Tol-APCs have potential therapeutic value for the treatment of rheumatoid arthritis as well as other autoimmune diseases.

The requirement of natural killer T-cells in tolerogenic APCs-mediated suppression of collagen-induced arthritis

TGF-beta-induced tolerogenic-antigen presenting cells (Tol-APCs) could induce suppression of autoimmune diseases such as collagen-induced arthritis (CIA) and allergic asthma. In contrast, many studies have shown that NKT cells are involved in the pathogenesis of Th1-mediated autoimmune joint inflammation and Th2-mediated allergic pulmonary inflammation. In this study, we investigated the effect of CD1d-restricted NKT cells in the Tol-APCs-mediated suppression of autoimmune disease using a murine CIA model. When CIA-induced mice were treated with Tol-APCs obtained from CD1d+/- or CD1d-/- mice, unlike CD1d+/- APCs, CD1d-/- Tol-APCs failed to suppress CIA. More specifically, CD1d-/- Tol-APCs failed to suppress the production of inflammatory cytokines and the induction of Th2 responses by antigen-specific CD4 T cells both in vitro and in vivo. Our results demonstrate that the presence of CD1d-restricted NKT cells is critical for the induction of Tol-APCs-mediated suppression of CIA.