Complex pattern of Th1 and Th2 activation with a preferential increase of autoreactive Th1 cells in BALB/c mice with proteoglycan (aggrecan)-induced arthritis.
The central role of CD4+ T cells and the balance between T helper (Th) subpopulations in the pathogenesis of autoimmune diseases have been extensively studied. Proteoglycan (aggrecan)-induced arthritis (PGIA) is a murine model for rheumatoid arthritis (RA), which is characterized by a Th1 dominance at the onset of the disease. In addition to CD4+ T cells, antigen-presenting B cells and autoantibodies seem to play an important role in the development and regulation of PGIA. To identify proteoglycan-specific CD4+ T cell subsets and Th1- and Th2-supported antibody isotypes during the progression of PGIA, spleen cells of proteoglycan-immunized BALB/c mice were harvested at different times of immunization, and at different stages of the disease, and their cytokine production and antigen-specific antibody isotype profiles were determined by enzyme-linked immunospot (ELISPOT) assays. Both Th1 and Th2 cytokine-producing cells, with the predominance of IL-4/IL-5-secreting cells, were detected during the prearthritic stage, and a shift toward a Th1 dominance was observed at the time of onset of arthritis. Tissue homogenates of acutely inflamed joints contained significantly higher levels of interferon-gamma than IL-4. The prearthritic period and both the acute and chronic phases of joint inflammation were characterized by IgG1 dominance in the sera and this correlated with the number of IgG1-secreting B cells in the spleen. However, the ratio of autoreactive IgG1/IgG2a-secreting cells decreased in arthritic animals. These results indicate the activation and possible regulatory roles of both Th1 and Th2 subsets in the autoimmune process, with the necessity of a relative increase of autoreactive Th1 cells for the induction of joint inflammation.
Holló
K
K
Department of Anatomy, Histology and Embryology, University Medical School of Debrecen, Debrecen, Hungary.
Glant
T T
TT
Garzó
M
M
Finnegan
A
A
Mikecz
K
K
Buzás
E
E
D053674:Aggrecans; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D001169:Arthritis, Experimental / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology*; D002358:Cartilage, Articular / Q000276:immunology / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000032:analysis / Q000097:blood / Q000276:immunology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D011509:Proteoglycans / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
C508320:Acan protein, mouse; D053674:Aggrecans; D000941:Antigens; D001324:Autoantigens; D011508:Chondroitin Sulfate Proteoglycans; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D037181:Lectins, C-Type; D011509:Proteoglycans