Presentation of arthritogenic peptide to antigen-specific T cells by fibroblast-like synoviocytes
| Autor: | Susan Kovats, Emily C. Somers, Judith Endres, Kevin C. Chung, Michael J. Davis, Laura A. Tesmer, Andrew G. Urquhart, Chinh N. Tran, Christopher D. Motyl, David A. Fox, Craig Smuda, Steven K. Lundy |
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| Rok vydání: | 2007 |
| Předmět: |
musculoskeletal diseases
T-Lymphocytes T cell CD58 CD40 Ligand Immunology Antigen presentation Antigen-Presenting Cells Mice Transgenic chemical and pharmacologic phenomena Major histocompatibility complex Autoantigens Arthritis Rheumatoid Interferon-gamma Mice Immune system Rheumatology Antigen Interferon Animals Humans Immunology and Allergy Medicine Pharmacology (medical) skin and connective tissue diseases Collagen Type II Cells Cultured Hybridomas biology business.industry Synovial Membrane Histocompatibility Antigens Class II Fibroblasts MHC restriction medicine.anatomical_structure CD4 Antigens biology.protein business medicine.drug |
| Zdroj: | Arthritis & Rheumatism. 56:1497-1506 |
| ISSN: | 1529-0131 0004-3591 |
| DOI: | 10.1002/art.22573 |
| Popis: | Objective. To assess the ability of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) to function as antigen-presenting cells (APCs) for arthritogenic autoantigens found within inflamed joint tissues. Methods. Human class II major histocompatibility complex (MHC)–typed FLS were used as APCs for murine class II MHC–restricted CD4 T cell hybridomas. Interferon- (IFN)–treated, antigen-loaded FLS were cocultured with T cell hybridomas specific for immunodominant portions of human cartilage gp-39 (HC gp-39) or human type II collagen (CII). T cell hybridoma activation was measured by enzyme-linked immunosorbent assay of culture supernatants for interleukin-2. Both synthetic peptide and synovial fluid (SF) were used as sources of antigen. APC function in cocultures was inhibited by using blocking antibodies to human class II MHC, CD54, or CD58, or to murine CD4, CD11a, or CD2. Results. Human FLS could present peptides from the autoantigens HC gp-39 and human CII to antigenspecific MHC-restricted T cell hybridomas. This response required pretreatment of FLS with IFN, showed MHC restriction, and was dependent on human class II MHC and murine CD4 for effective antigen presentation. Furthermore, FLS were able to extract and present antigens found within human SF to both the HC gp-39 and human CII T cell hybridomas in an IFN-dependent and MHC-restricted manner. Conclusion. RA FLS can function as APCs and are able to present peptides derived from autoantigens found within joint tissues to activated T cells in vitro. In the context of inflamed synovial tissues, FLS may be an important and hitherto overlooked subset of APCs that could contribute to autoreactive immune responses. |
| Databáze: | OpenAIRE |
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