title: Lack of CD80 expression by fibroblast-like synoviocytes leading to anergy in T lymphocytes.
abstract: OBJECTIVE
  To investigate whether contact with HLA-DR+, but CD80-, fibroblast-like synoviocytes (FLS) in the presence of antigen leads to the induction of anergy in, rather than stimulation of, T cells.
  
  
  METHODS
  Cell surface expression of activation and costimulatory markers on FLS were studied by flow cytometry. Functional changes were investigated by T cell proliferation to tuberculin purified protein derivative or allogeneic responses to FLS, in the presence or absence of DAP3.B7 cells, a human CD80-transfected mouse fibroblast cell line. Induction of anergy was investigated by a 2-stage culture system. T cells were cocultured with allogeneic FLS in the primary culture, rested, and restimulated in the secondary culture by FLS in the presence or absence of DAP3.B7 cells or interleukin-2 (IL-2).
  
  
  RESULTS
  Direct contact between T cells and FLS caused up-regulation of CD69 on T cells and HLA-DR on FLS in both the allogeneic and autologous cultures. The addition of DAP3.B7 cells to FLS-T cell cocultures restored the depressed allogeneic responses of T cells. The allogeneic response by T cells to FLS in the presence of DAP3.B7 cells could be completely inhibited by blocking CD80 with CTLA-4 Ig. Indirect evidence that T cells cocultured with FLS were anergic was the up-regulation of CD25, negligible T cell proliferation, and the restoration of proliferation by the addition of exogenous IL-2. Direct evidence of anergy was obtained when T cells from the primary cultures with FLS remained unresponsive to secondary culture with FLS even in the presence of DAP3.B7 cells. In contrast, primary culture of T cells with FLS plus DAP3.B7 cells initiated a good allogeneic response in all subsequent cultures.
  
  
  CONCLUSIONS
  It is possible that T cells within the synovium may be anergized by contact with HLA-DR+ CD80- FLS.
authors.affiliation: Department of Rheumatology, GKT Medical Schools, Guy's Hospital, London, UK.
authors.forename: V M
authors.initials: VM
authors.lastname: Corrigall
authors.forename: E
authors.initials: E
authors.lastname: Solau-Gervais
authors.forename: G S
authors.initials: GS
authors.lastname: Panayi
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018122:B7-1 Antigen / Q000378:metabolism*; D002460:Cell Line; D017635:Clonal Anergy; D018920:Coculture Techniques; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014162:Transfection; D014373:Tuberculin / Q000494:pharmacology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D006684:HLA-DR Antigens; D007371:Interferon-gamma; D007376:Interleukin-2; D037181:Lectins, C-Type; D014373:Tuberculin; D000099192:CD69 Antigens