Presentation of arthritogenic peptide to antigen-specific T cells by fibroblast-like synoviocytes
Chinh N. Tran
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorMichael J. Davis
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorLaura A. Tesmer
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorJudith L. Endres
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorChristopher D. Motyl
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorCraig Smuda
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorEmily C. Somers
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorKevin C. Chung
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorAndrew G. Urquhart
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorSteven K. Lundy
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorCorresponding Author
David A. Fox
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
University of Michigan, Room 3918 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0358Search for more papers by this authorChinh N. Tran
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorMichael J. Davis
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorLaura A. Tesmer
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorJudith L. Endres
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorChristopher D. Motyl
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorCraig Smuda
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorEmily C. Somers
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorKevin C. Chung
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorAndrew G. Urquhart
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorSteven K. Lundy
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
Search for more papers by this authorCorresponding Author
David A. Fox
University of Michigan Rheumatic Disease Core Center, Ann Arbor
University of Michigan Medical School, Ann Arbor
University of Michigan, Room 3918 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0358Search for more papers by this authorAbstract
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-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.
Results
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.
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.
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