Presentation of arthritogenic peptide to antigen-specific T cells by fibroblast-like synoviocytes
Article first published online: 27 APR 2007
Copyright © 2007 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 56, Issue 5, pages 1497–1506, May 2007
How to Cite
Tran, C. N., Davis, M. J., Tesmer, L. A., Endres, J. L., Motyl, C. D., Smuda, C., Somers, E. C., Chung, K. C., Urquhart, A. G., Lundy, S. K., Kovats, S. and Fox, D. A. (2007), Presentation of arthritogenic peptide to antigen-specific T cells by fibroblast-like synoviocytes. Arthritis & Rheumatism, 56: 1497–1506. doi: 10.1002/art.22573
- Issue published online: 27 APR 2007
- Article first published online: 27 APR 2007
- Manuscript Accepted: 29 JAN 2007
- Manuscript Received: 13 JUL 2006
- University of Michigan Rheumatic Disease Core Center
- NIH. Grant Numbers: AR-38477, AR-048310
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.
Human class II major histocompatibility complex (MHC)–typed FLS were used as APCs for murine class II MHC–restricted CD4 T cell hybridomas. Interferon-γ (IFNγ)–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.
Human FLS could present peptides from the autoantigens HC gp-39 and human CII to antigen-specific MHC-restricted T cell hybridomas. This response required pretreatment of FLS with IFNγ, 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 IFNγ-dependent and MHC-restricted manner.
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.