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.
Banerjee
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Shriners Hospital for Crippled Children, Department of Surgery, McGill University, Montreal, Quebec, Canada.
Webber
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C
Poole
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AR
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