Gewählte Publikation:
Rappl, G; Kapsokefalou, A; Heuser, C; Rössler, M; Ugurel, S; Tilgen, W; Reinhold, U; Abken, H.
Dermal fibroblasts sustain proliferation of activated T cells via membrane-bound interleukin-15 upon long-term stimulation with tumor necrosis factor-alpha.
J Invest Dermatol. 2001; 116(1):102-109
Doi: 10.1046/j.1523-1747.2001.00239.x
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- Co-Autor*innen der Med Uni Graz
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Ugurel-Becker Selma
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- Abstract:
- In chronic inflammatory conditions, mononuclear cells infiltrate the connective tissue attracted by fibroblast-secreted chemokines. The role of fibroblasts in sustaining the lymphocyte immune response upon cellular infiltration is so far unresolved. We here report that, upon prolonged stimulation with tumor necrosis factor-alpha, dermal fibroblasts enhance proliferation of activated T cells whereas unstimulated fibroblasts do not. T cell growth stimulation requires cell contact of tumor necrosis factor-alpha stimulated fibroblasts to T cells and is not due to soluble factors. Growth stimulation is substantially blocked by neutralizing antibodies to interleukin-15. Fluorescence-activated cell sorter analyses revealed that tumor necrosis factor alpha stimulated fibroblasts expose interleukin-15 in a membrane-bound form on the cell surface whereas nonstimulated fibroblasts and interferon-gamma treated fibroblasts do not. The amount of membrane interleukin-15 increases with the duration of tumor necrosis factor-alpha stimulation for at least 3 d. Unstimulated fibroblasts, however, accumulate interleukin-15 in the cytoplasm. No interleukin-15 could be detected in the culture supernatant. Immunohistochemical analyses confirmed membrane interleukin-15 on dermal fibroblasts in discoid lupus erythematosus skin lesions whereas no membrane interleukin-15 was found on the surface of fibroblasts in healthy skin. We conclude that dermal fibroblasts upon long-term tumor necrosis factor-alpha stimulation during chronic inflammation are involved via membrane-bound interleukin-15 in stimulating proliferation of accumulated, activated T cells.
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Antibodies -
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Cell Division - physiology
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Cell Membrane - chemistry
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Fibroblasts - cytology
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Humans -
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Immunoenzyme Techniques -
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Interleukin-15 - genetics Interleukin-15 - immunology Interleukin-15 - pharmacology
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Lupus Erythematosus, Discoid - pathology
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Lymphocyte Activation - drug effects
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RNA, Messenger - metabolism
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Reverse Transcriptase Polymerase Chain Reaction -
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Skin - cytology
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T-Lymphocytes - immunology
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Time Factors -
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Tumor Necrosis Factor-alpha - pharmacology
- Find related publications in this database (Keywords)
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cell-to-cell interactions
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human fibroblasts
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inflammation