ANTI-CD8 TREATMENT REDUCES THE SEVERITY OF INFLAMMATORY ARTHRITIS, BUT NOT VASCULITIS, IN MERCURIC CHLORIDE-INDUCED AUTOIMMUNITY

Mercuric chloride (HgCl2) induces a T cell-dependent autoimmune syndro me in Brown-Norway (BN) rats characterized by a humoral response, tiss ue injury with an accumulation of CD8(+) and CD4(+) T cells, and an in crease in tissue IL-4 mRNA and serum IgE suggesting Th2 cell activatio n. In other models of autoimmune disease, CD8(+) cells act in both ant i- and pro-inflammatory capacities, suggesting that functionally disti nct CD8(+) populations exist in vivo. The effect of treatment with OX8 , a depleting anti-CD8 MoAb, on the initiation of HgCl2-induced autoim munity was assessed in two experiments in a total of 20 BN rats, and c ompared with 20 animals treated with a control MoAb or PBS. OX8 signif icantly 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-ind uced arthritis was significantly reduced in OX8-treated animals; media n 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 exac erbated the early rise in HgCl2-induced IgE and induced a significant rise in plasma interferon-gamma (IFN-gamma), suggesting that CD8(+) ce lls may have a regulatory influence on Th cell populations. These data provide direct evidence that CD8(+) cells may act in a proinflammator y capacity in both this model of autoimmunity and the pathogenesis of inflammatory arthritis.