The progression of the inflammation in established collagen‐induced arthritis can be altered by treatments with immunological or pharmacological agents which inhibit T cell activities

Abstract

Alterations in the progression of the inflammatory disease in mice with established collagen-induced arthritis (CIA) by in vivo treatments with either anti-T cell antibodies or an immunosuppressive drug, whose main targets of action are T cells, were studied. It was demonstrated that the in vivo administration of either monoclonal anti-L3T4, anti-Ly-2 or the combination of anti-L3T4 and anti-Ly-2 failed to modify the inflammatory disease after the arthritis had been initiated. Nevertheless, the progression of disease was decreased by treatments with rabbit anti-mouse lymphocyte sera (ALS) in mice with established CIA. While there was a substantial reduction in the proliferative responses to the T cell mitogen concanavalin A (Con A) in these ALS-treated mice, proliferation to a B cell mitogen, lipopolysaccharide, was unaffected. Furthermore, treatments with anti-Thy-1.2 monoclonal antibody (mAb) by itself did not alter the progression of the ongoing inflammatory disease, but combined treatments with both anti-Thy-1.2 and anti-L3T4 mAb prevented the further advancement of the arthritic disease. Although mice receiving either anti-Thy-1.2 alone or both anti-Thy-1.2 and anti-L3T4 exhibited complete absence of Thy-1+ cells within their inguinal lymph nodes, the proliferative responses to Con A by LN cells from mice treated with the combination of anti-Thy-1.2 and anti-L3T4 were drastically reduced compared to the responses of either the anti-Thy-1.2 or anti-L3T4-treated groups. Finally, daily treatments with cyclosporin A, an immunosuppressive drug which preferentially acts on T cells, were also effective in modifying the clinical course of the arthritic disease in mice with established CIA. These results suggest that immunocompetent cells which express the Thy-1 surface marker, most likely Thy-1+ T cells, may play a role in maintaining and perpetuating the inflammatory disease of established CIA.

Treatment with an anti-CD4 monoclonal antibody strongly ameliorates established rat adjuvant arthritis

“…Van den Broek et al [28] reported a decrease in paw swelling when administering W3/25 to rats with established streptococcal cell wall-induced arthritis. In contrast, anti-CD4 MoAbs were unable to ameliorate established CIA in mice [15][16][17] or in rats [29].…”

“…Nevertheless, the disappearance of CD8 lymphocytes did not influence the chronic inflammatory response. Antibodies against CD8 molecule are also ineffective in the prevention of rat AA [31] and mouse CIA [16]. CD8 cells do not seem therefore to regulate the inflammatory response, either in the initiation or in the perpetuation of an arthritic disease.…”

Exacerbation of Established Collagen‐Induced Arthritis in Mice Treated with An Anti—T Cell Receptor Antibody

“…Contrasting results, implicating an active role of T cells in established CIA, have been proposed by Horn et a1 (12), who demonstrated that combined treatment with anti-CD4 MAb and anti-Thy-1 MAb, begun after the establishment of arthritis, prevented further advancement of the disease. In addition, Seki et a1 (3) suggested that both anti-CII antibody and cellular immunity are required for the development and perpetuation of CIA.…”

Anti-CD8 treatment reduces the severity of inflammatory arthritis, but not vasculitis, in mercuric chloride-induced autoimmunity

“…The resistant Buffalo strain is reported to have a significantly lower CD4/CD8 ratio in blood, spleen and lymph node compared with the susceptible Holtzman strain, and selective depletion of CD8 + cells (with low dose cyclophosphamide) in Buffalo rats induces AA, suggesting an anti-inflammatory role for CD8 + cells in this strain [35]. In collagen-induced arthritis, although CD8 + cells are found to accumulate in rat synovial sections, anti-CD8 therapy has no effect on established arthritis in mice [36,37] but reduces the severity of arthritis in castrated female rats, suggesting a proinflammatory role in this instance [38].…”