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

Abstract

Mercuric chloride (HgCl₂) induces a T cell-dependent autoimmune syndrome in Brown-Norway (BN) rats characterized by a humoral response, tissue injury with an accumulation of CD8⁺ and CD4⁺ T cells, and an increase in tissue IL-4 mRNA and serum IgE suggesting Th2 cell activation. In other models of autoimmune disease, CD8⁺ cells act in both anti-and pro-inflammatory capacities, suggesting that functionally distinct CD8⁺ populations exist in vivo. The effect of treatment with OX8, a depleting anti-CD8 MoAb, on the initiation of HgCl₂-induced autoimmunity was assessed in two experiments in a total of 20 BN rats, and compared with 20 animals treated with a control MoAb or PBS. OX8 significantly depleted peripheral blood CD8⁺ lymphocytes, had no effect on HgCl₂-induced anti-collagen or myeloperoxidase antibodies, nor on the incidence or severity of caecal vasculitis. The severity of HgCl₂-induced arthritis was significantly reduced in OX8-treated animals; median peak score reduced from 7.5 to 3.0 (experiment 1) and from 7.0 to 4 (experiment 2) (P = 0.009, Mann–Whitney U-test). OX8 treatment also exacerbated the early rise in HgCl₂-induced IgE and induced a significant rise in plasma interferon-gamma (IFN-γ), suggesting that CD8⁺ cells may have a regulatory influence on Th cell populations. These data provide direct evidence that CD8⁺ cells may act in a proinflammatory capacity in both this model of autoimmunity and the pathogenesis of inflammatory arthritis.

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