Lack of CD80 expression by fibroblast-like synoviocytes leading to anergy in T lymphocytes

V M Corrigall, E Solau-Gervais, G S Panayi

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32 Citations (Scopus)

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. Conclusion. It is possible that T cells within the synovium may be anergized by contact with HLA-DR+ CD80- FLS.
Original languageEnglish
Pages (from-to)1606 - 1615
Number of pages10
JournalArthritis & Rheumatism
Volume43
Issue number7
DOIs
Publication statusPublished - Jul 2000

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