Antigen-presenting capacity of rheumatoid synovial fibroblasts
In normal, healthy joints, synovial fibroblasts do not express major histocompatibility complex (MHC) class II molecules. However, in inflamed joints of rheumatoid arthritis (RA) patients, synovial fibroblasts show an abundant expression of MHC class II. Does this increase in expression have functio...
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| Published in: | Immunology Vol. 82; no. 2; p. 268 |
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| Main Authors: | , , |
| Format: | Journal Article |
| Language: | English |
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01.06.1994
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| ISSN: | 0019-2805 |
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| Abstract | In normal, healthy joints, synovial fibroblasts do not express major histocompatibility complex (MHC) class II molecules. However, in inflamed joints of rheumatoid arthritis (RA) patients, synovial fibroblasts show an abundant expression of MHC class II. Does this increase in expression have functional consequences for antigen presentation to T cells? To date, the precise role of synovial fibroblasts in antigen presentation has not been documented. Here, we show by three different examples that cultured synovial fibroblasts with interferon-gamma (IFN-gamma)-induced MHC class II expression are capable of processing soluble protein for presentation to CD4+ T cells. First, the antigen-presenting cell (APC) function of synovial fibroblasts was studied in an autologous model. From synovial tissue of a RA patient both a fibroblast cell line and a tetanus toxoid (TT)-specific CD4+ T-cell line were generated. A dose-dependent TT response was observed only when TT was presented by IFN-gamma-pretreated synovial fibroblasts. As more direct evidence for MHC class II-restricted antigen presentation, the response of a Mycobacterium tuberculosis-specific CD4+ T-cell clone isolated from rheumatoid synovial fluid was demonstrated in the presence of synovial fibroblasts. The response was DR4Dw4-restricted and could be inhibited by monoclonal antibody (mAb) to HLA-DR. In addition, the lymphokine secretion pattern of the synovial T-cell clone did not differ qualitatively upon antigen-specific stimulation using peripheral blood mononuclear cells (PBMC) or synovial fibroblasts as APC. In order to provide evidence for intracellular antigen processing we next examined the response of a M. leprae-specific T-cell clone with known epitope specificity. Our data suggest that synovial fibroblasts are not passive bystanders, but can become active participants in the development and maintenance of chronic inflammation. |
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| AbstractList | In normal, healthy joints, synovial fibroblasts do not express major histocompatibility complex (MHC) class II molecules. However, in inflamed joints of rheumatoid arthritis (RA) patients, synovial fibroblasts show an abundant expression of MHC class II. Does this increase in expression have functional consequences for antigen presentation to T cells? To date, the precise role of synovial fibroblasts in antigen presentation has not been documented. Here, we show by three different examples that cultured synovial fibroblasts with interferon-gamma (IFN-gamma)-induced MHC class II expression are capable of processing soluble protein for presentation to CD4+ T cells. First, the antigen-presenting cell (APC) function of synovial fibroblasts was studied in an autologous model. From synovial tissue of a RA patient both a fibroblast cell line and a tetanus toxoid (TT)-specific CD4+ T-cell line were generated. A dose-dependent TT response was observed only when TT was presented by IFN-gamma-pretreated synovial fibroblasts. As more direct evidence for MHC class II-restricted antigen presentation, the response of a Mycobacterium tuberculosis-specific CD4+ T-cell clone isolated from rheumatoid synovial fluid was demonstrated in the presence of synovial fibroblasts. The response was DR4Dw4-restricted and could be inhibited by monoclonal antibody (mAb) to HLA-DR. In addition, the lymphokine secretion pattern of the synovial T-cell clone did not differ qualitatively upon antigen-specific stimulation using peripheral blood mononuclear cells (PBMC) or synovial fibroblasts as APC. In order to provide evidence for intracellular antigen processing we next examined the response of a M. leprae-specific T-cell clone with known epitope specificity. Our data suggest that synovial fibroblasts are not passive bystanders, but can become active participants in the development and maintenance of chronic inflammation. In normal, healthy joints, synovial fibroblasts do not express major histocompatibility complex (MHC) class II molecules. However, in inflamed joints of rheumatoid arthritis (RA) patients, synovial fibroblasts show an abundant expression of MHC class II. Does this increase in expression have functional consequences for antigen presentation to T cells? To date, the precise role of synovial fibroblasts in antigen presentation has not been documented. Here, we show by three different examples that cultured synovial fibroblasts with interferon-gamma (IFN-gamma)-induced MHC class II expression are capable of processing soluble protein for presentation to CD4+ T cells. First, the antigen-presenting cell (APC) function of synovial fibroblasts was studied in an autologous model. From synovial tissue of a RA patient both a fibroblast cell line and a tetanus toxoid (TT)-specific CD4+ T-cell line were generated. A dose-dependent TT response was observed only when TT was presented by IFN-gamma-pretreated synovial fibroblasts. As more direct evidence for MHC class II-restricted antigen presentation, the response of a Mycobacterium tuberculosis-specific CD4+ T-cell clone isolated from rheumatoid synovial fluid was demonstrated in the presence of synovial fibroblasts. The response was DR4Dw4-restricted and could be inhibited by monoclonal antibody (mAb) to HLA-DR. In addition, the lymphokine secretion pattern of the synovial T-cell clone did not differ qualitatively upon antigen-specific stimulation using peripheral blood mononuclear cells (PBMC) or synovial fibroblasts as APC. In order to provide evidence for intracellular antigen processing we next examined the response of a M. leprae-specific T-cell clone with known epitope specificity. Our data suggest that synovial fibroblasts are not passive bystanders, but can become active participants in the development and maintenance of chronic inflammation.In normal, healthy joints, synovial fibroblasts do not express major histocompatibility complex (MHC) class II molecules. However, in inflamed joints of rheumatoid arthritis (RA) patients, synovial fibroblasts show an abundant expression of MHC class II. Does this increase in expression have functional consequences for antigen presentation to T cells? To date, the precise role of synovial fibroblasts in antigen presentation has not been documented. Here, we show by three different examples that cultured synovial fibroblasts with interferon-gamma (IFN-gamma)-induced MHC class II expression are capable of processing soluble protein for presentation to CD4+ T cells. First, the antigen-presenting cell (APC) function of synovial fibroblasts was studied in an autologous model. From synovial tissue of a RA patient both a fibroblast cell line and a tetanus toxoid (TT)-specific CD4+ T-cell line were generated. A dose-dependent TT response was observed only when TT was presented by IFN-gamma-pretreated synovial fibroblasts. As more direct evidence for MHC class II-restricted antigen presentation, the response of a Mycobacterium tuberculosis-specific CD4+ T-cell clone isolated from rheumatoid synovial fluid was demonstrated in the presence of synovial fibroblasts. The response was DR4Dw4-restricted and could be inhibited by monoclonal antibody (mAb) to HLA-DR. In addition, the lymphokine secretion pattern of the synovial T-cell clone did not differ qualitatively upon antigen-specific stimulation using peripheral blood mononuclear cells (PBMC) or synovial fibroblasts as APC. In order to provide evidence for intracellular antigen processing we next examined the response of a M. leprae-specific T-cell clone with known epitope specificity. Our data suggest that synovial fibroblasts are not passive bystanders, but can become active participants in the development and maintenance of chronic inflammation. |
| Author | Boots, A M Rijnders, A W Wimmers-Bertens, A J |
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| References_xml | – reference: 2481588 - Eur J Immunol. 1989 Dec;19(12):2237-42 – reference: 3934267 - J Immunol. 1985 Dec;135(6):3750-62 – reference: 87477 - J Immunol. 1979 Jul;123(1):342-9 – reference: 2271017 - N Engl J Med. 1990 May 3;322(18):1277-89 – reference: 6980416 - Proc Natl Acad Sci U S A. 1982 Jun;79(11):3632-6 – reference: 2185780 - Immunol Today. 1990 Feb;11(2):49-55 – reference: 307029 - J Immunol. 1978 Jun;120(6):2027-32 – reference: 2311298 - Clin Exp Immunol. 1990 Feb;79(2):189-94 – reference: 1903707 - Eur J Immunol. 1991 May;21(5):1297-302 – reference: 1657009 - Arthritis Rheum. 1991 Sep;34(9):1094-105 – reference: 2993365 - J Clin Invest. 1985 Aug;76(2):837-48 – reference: 2272662 - Immunogenetics. 1990;32(6):413-8 – reference: 2442194 - J Clin Invest. 1987 Sep;80(3):595-604 – reference: 2180403 - Arthritis Rheum. 1990 Mar;33(3):305-15 – reference: 3157869 - Nature. 1985 Apr 11-17;314(6011):537-9 – reference: 1997647 - J Exp Med. 1991 Mar 1;173(3):569-74 – reference: 2580020 - J Immunol. 1985 May;134(5):3233-40 – reference: 3098840 - J Immunol. 1987 Jan 15;138(2):385-92 – reference: 6966655 - J Immunol. 1980 Jul;125(1):293-9 – reference: 1690768 - J Immunol. 1990 Apr 1;144(7):2459-64 – reference: 1380043 - J Immunol. 1992 Aug 15;149(4):1424-31 – reference: 2504878 - J Exp Med. 1989 Sep 1;170(3):865-75 – reference: 1701992 - Arthritis Rheum. 1990 Dec;33(12):1776-86 – reference: 1732419 - J Exp Med. 1992 Feb 1;175(2):613-6 – reference: 2442197 - J Clin Invest. 1987 Sep;80(3):786-96 – reference: 3358796 - Arthritis Rheum. 1988 Mar;31(3):315-24 |
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| SubjectTerms | Antigen-Presenting Cells - immunology Antigens, Bacterial - immunology Antigens, Surface - analysis Arthritis, Rheumatoid - immunology Cell Line Cells, Cultured Dose-Response Relationship, Immunologic Fibroblasts - immunology HLA-DR Antigens - analysis Humans Interferon-gamma - immunology Recombinant Proteins Synovial Membrane - immunology Tetanus Toxoid - immunology |
| Title | Antigen-presenting capacity of rheumatoid synovial fibroblasts |
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