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 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-gamma), 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.
Kiely
P D
PD
Division of Renal Medicine, St George's Hospital Medical School, London, UK.
O'Brien
D
D
Oliveira
D B
DB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001168:Arthritis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D001323:Autoantibodies / Q000032:analysis; D015551:Autoimmunity / Q000187:drug effects*; D016827:CD8 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002429:Cecal Diseases / Q000139:chemically induced / Q000276:immunology; D003094:Collagen / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D007073:Immunoglobulin E / Q000032:analysis; D007371:Interferon-gamma / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000276:immunology; D008627:Mercuric Chloride / Q000633:toxicity*; D009195:Peroxidase / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D014657:Vasculitis / Q000139:chemically induced* / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D016827:CD8 Antigens; D007073:Immunoglobulin E; D008627:Mercuric Chloride; D007371:Interferon-gamma; D003094:Collagen; D009195:Peroxidase