Absence of in vitro responses to type II collagen by splenocytes from arthritic BALB/c mice is possibly caused by intrinsic CD25+ regulatory cells.
Collagen-induced arthritis-resistant BALB/c mice develop arthritis if a foreign protein is added to an emulsion of type II collagen (CII) and adjuvant. The IgG autoantibody activity to CII is increased, whereas no CII autoreactive T cells in vitro can be recorded. In this study, we have explored whether CD25+ cells inhibit T-cell autoreactivity to CII. We also followed the IgG anti-CII autoantibody activity and the IL-6 level in serum during the development of arthritis. BALB/c mice were coimmunized with bovine CII (BCII) and keyhole limpet haemocyanin (KLH) in complete Freund's adjuvant and boostered 3 weeks later. Control animals were immunized with either BCII or KLH. Sera were collected prior to and during the development of arthritis and examined for IgG anti-CII antibody activity and IL-6 content. When all BCII-KLH immunized mice had developed arthritis, splenocytes were prepared, with and without CD25+ cells, and tested for BCII reactivity in vitro. The serum IgG, IgG1 and IgG2a anti-CII antibody activities and the IL-6 level were significantly higher in BCII-KLH immunized mice than in BCII-immunized animals that failed to develop arthritis. The BCII-specific IL-2 secretion in vitro was significantly increased in CD25-depleted splenocyte cultures prepared from arthritic BCII-KLH-immunized mice. Development of arthritis in BALB/c mice induced by coimmunization with BCII/KLH results in increased levels of circulating IL-6 and IgG autoantibodies to CII. The arthritogenic BCII-KLH immunization potentiates BCII-specific IL-2 secretion by CD25-depleted splenocytes, but CD25+ cells hamper the outcome of their action, at least in vitro.
Bäckström
F
F
Faculty of Odontology, Section of Oral Microbiology and Immunology, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
Dahlgren
U
U
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000918:Antibody Specificity; D001169:Arthritis, Experimental / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D002478:Cells, Cultured; D024043:Collagen Type II / Q000008:administration & dosage / Q000276:immunology*; D006433:Hemocyanins / Q000494:pharmacology; D007114:Immunization; D007115:Immunization Schedule; D007074:Immunoglobulin G / Q000276:immunology; D007279:Injections, Subcutaneous; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000276:Adjuvants, Immunologic; D001323:Autoantibodies; D024043:Collagen Type II; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin