Dermal fibroblasts sustain proliferation of activated T cells via membrane-bound interleukin-15 upon long-term stimulation with tumor necrosis factor-alpha.
Dermal fibroblasts sustain proliferation of activated T cells via membrane-bound interleukin-15 upon long-term stimulation with tumor necrosis factor-alpha.
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在肿瘤坏死因子-α 的长期刺激下，真皮成纤维细胞通过膜结合白细胞介素 15 维持活化 T 细胞的增殖。
DOI：
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发表时间：
2001
影响因子：
6.5
通讯作者：
U. Reinhold
中科院分区：
文献类型：
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作者：
Anna Kapsokefalou;C. Heuser;H. Abken;G. Rappl;Martin Röβler;S. Ugurel;W. Tilgen;U. Reinhold
在慢性炎症条件下，单核细胞在成纤维细胞分泌的趋化因子的吸引下浸润结缔组织。成纤维细胞在细胞浸润后维持淋巴细胞免疫反应中的作用迄今尚未解决。我们在此报告称，在肿瘤坏死因子-α 的长期刺激下，真皮成纤维细胞会增强活化 T 细胞的增殖，而未刺激的成纤维细胞则不会。 T 细胞生长刺激需要肿瘤坏死因子-α 刺激的成纤维细胞与 T 细胞的细胞接触，而不是由于可溶性因子。白细胞介素 15 的中和抗体可显着阻断生长刺激。荧光激活细胞分选仪分析显示，肿瘤坏死因子 α 刺激的成纤维细胞会在细胞表面以膜结合形式暴露白细胞介素 15，而未刺激的成纤维细胞和干扰素 γ 处理的成纤维细胞则不会。膜白细胞介素15的量随着肿瘤坏死因子-α刺激至少3天的持续时间而增加。然而，未受刺激的成纤维细胞会在细胞质中积聚白细胞介素 15。培养上清液中未检测到白细胞介素15。免疫组织化学分析证实，盘状红斑狼疮皮肤病变的真皮成纤维细胞上存在膜白细胞介素 15，而健康皮肤的成纤维细胞表面未发现膜白细胞介素 15。我们得出的结论是，在慢性炎症过程中，真皮成纤维细胞在长期肿瘤坏死因子-α刺激下，通过膜结合的白细胞介素-15参与刺激累积的活化T细胞的增殖。
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.
影响因子：
29.4
作者：
Reinecker, HC;MacDermott, RP;Podolsky, DK
通讯作者：
Podolsky, DK
Interleukin-1 和转化生长因子-α：金属蛋白酶、PGE2 和人成纤维细胞增殖的协同刺激。
影响因子：
3.7
作者：
Unemori,EN;Ehsani,N;Wang,M;Lee,S;McGuire,J;Amento,EP
通讯作者：
Amento,EP