Retrobulbar fibroblasts from patients with Graves' ophthalmopathy induce downregulation of APO-1 in T lymphocytes and protect T cells from apoptosis during coculture.
Retrobulbar fibroblasts are a main target of the immune process in Graves' ophthalmopathy (GO) and have been shown to have unique metabolic qualities. The aim of our study was to analyze the immunoregulatory properties of retrobulbar fibroblasts and particularly whether fibroblasts were able to protect T cells from apoptosis. Retrobulbar fibroblasts from patients with GO spontaneously expressed higher concentrations of HLA class I and HLA class II (p<0.05) than control cells, whereas basal CD54 expression was unimpaired. Stimulation with IFN gamma led to a more pronounced increase in HLA class I, class II and CD54 in autoimmune fibroblasts than in control cells (p<0.05). Fibroblasts from both groups had the capacity to prevent apoptosis in preactivated peripheral T cells during coculture. T cell survival was, however, more pronounced after coculture with retrobulbar fibroblasts than with control cells (p<0.05). Prevention of T cell death was associated with a decreased expression of APO-1 on the T cell surface, whereas the bcl-2 expression of the T cells remained unchanged. Our results suggest that the increased expression of immunoregulatory molecules combined with a pronounced capacity of autoimmune fibroblasts to protect infiltrating T cells from apoptosis might at least partly explain the site selectivity as well as the perpetuation of the extrathyroidal manifestation of Graves' disease.
Mohácsi
A
A
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria.
Trieb
K
K
Anderl
H
H
Grubeck-Loebenstein
B
B
D017209:Apoptosis / Q000276:immunology; D015551:Autoimmunity; D002478:Cells, Cultured; D015536:Down-Regulation; D005347:Fibroblasts / Q000276:immunology; D006111:Graves Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019014:fas Receptor / Q000378:metabolism*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015375:Receptors, Interleukin-2; D019014:fas Receptor; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma