Interferon-gamma but not granulocyte/macrophage colony-stimulating factor augments proteoglycan presentation by synovial cells and chondrocytes to an autopathogenic T cell hybridoma.
Immunization of BALB/c mice with human cartilage proteoglycan (aggrecan) produces a progressive polyarthritis, similar in many aspects to human rheumatoid arthritis, and autoreactive T cells are necessary for initiation of the disease. To study the immunopathological mechanisms operating in the synovium of arthritic mice, we isolated a proteoglycan (PG)-specific arthritogenic T-cell hybridoma, 5/4E8, and examined the presentation of PG to this T-cell hybridoma by mouse synovial cells and chondrocytes. Both cell types expressed very low levels of major histocompatibility complex (MHC) class II following isolation and culture and were unable to present PG to the hybridoma. However, following stimulation with interferon-gamma (IFN-gamma), both synovial cells and chondrocytes showed a marked increase in MHC class II expression and consequently were able to present PG very effectively. The PG-specific responses of the hybridoma were abrogated by an anti-Ia monoclonal antibody. Granulocyte-macrophage colony-stimulating factor (GM-CSF), one of the most abundant cytokines in the rheumatoid synovium, had no effect on the antigen-presenting capacity of synovial cells and chondrocytes, either on its own or together with IFN gamma.
Brennan
F R
FR
Department of Biochemistry, Rush Medical University, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA.
Mikecz
K
K
Buzás
E I
EI
Glant
T T
TT
D053674:Aggrecans; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D001168:Arthritis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006825:Hybridomas / Q000276:immunology*; D007114:Immunization; D007371:Interferon-gamma / Q000494:pharmacology*; D037181:Lectins, C-Type; D051379:Mice; D008807:Mice, Inbred BALB C; D011509:Proteoglycans / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D011994:Recombinant Proteins; D013268:Stimulation, Chemical; D013583:Synovial Membrane / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
C508320:Acan protein, mouse; C508321:Acan protein, rat; D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D037181:Lectins, C-Type; D011509:Proteoglycans; D011994:Recombinant Proteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor