The induction of arthritis in mice by the cartilage proteoglycan aggrecan: roles of CD4+ and CD8+ T cells.
Peripheral arthritis is produced in BALB/c mice after hyperimmunization with the cartilage proteoglycan aggrecan (PG). Adoptive transfer studies have suggested the roles of T cells including CD8+ T cells in the disease process. To evaluate the roles of CD4+ and CD8+ T cell subsets in vivo in the induction of this disease by immunization, PG-immunized mice were treated with isotype-controlled rat IgG2b monoclonal anti-CD4 or anti-CD8 antibodies, or were left untreated. CD4+ T cell depletion resulted in total inhibition of the disease with markedly decreased anti-PG antibody responses. CD8+ T cell depletion, however, significantly enhanced the severity of the disease without affecting peak anti-PG antibodies, as compared to the control mice. These results demonstrate a crucial role for CD4+ T cells in the pathogenesis of this disease. However, CD8+ T cells do not seem to be required for the induction of arthritis by immunization but instead may play an immunoregulatory role.
Shriners Hospital for Crippled Children, Department of Surgery, McGill University, Montreal, Quebec, Canada.
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Banerjee
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Webber
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Poole
D053674:Aggrecans; D000818:Animals; D000906:Antibodies / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000209:etiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D016827:CD8 Antigens / Q000032:analysis*; D002356:Cartilage / Q000276:immunology*; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins; D005260:Female; D037181:Lectins, C-Type; D051379:Mice; D008807:Mice, Inbred BALB C; D011509:Proteoglycans / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000502:physiology*
C508320:Acan protein, mouse; C508321:Acan protein, rat; D053674:Aggrecans; D000906:Antibodies; D016827:CD8 Antigens; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans