Presentation of arthritogenic peptide to antigen-specific T cells by fibroblast-like synoviocytes

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 11 major histocompatibility complex (MHC)-typed FLS were used as APCs for murine class 11 MHC-restricted CD4 T cell hybridomas. Interferon-y (IFNy)-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 11 collagen (CH). 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 11 NIHG, CD54, or CD58, or to murine CD4, CD11a, or CD2. Results. Human FLS could present peptides from the autoantigens HC gp-39 and human CH to antigen-specific MHC-restricted T cell hybridomas. This response required pretreatment of FLS with IFNy, showed MHC restriction, and was dependent on human class 11 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 CH T cell hybridomas in an IFN-y-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.