Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-alpha production in rheumatoid arthritis
Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-alpha production in rheumatoid arthritis
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DOI：
10.1038/nm0297-189
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发表时间：
1997-02-01
期刊：
影响因子：
82.9
通讯作者：
Liew, FY
中科院分区：
文献类型：
--
作者：
McInnes, IB;Leung, BP;Liew, FY
肿瘤坏死因子-α在类风湿性关节炎（RA）发病机制中占据中心作用。我们现在报道，白细胞介素-15（IL-15）可以通过激活滑膜T细胞诱导RA产生TNF-α。由IL-15激活的外周血（PB）T细胞通过细胞接触依赖性机制诱导巨噬细胞产生显著的TNF-α。新鲜分离的RA滑膜T细胞具有类似的能力，在体外，IL-15是必要的，以维持这种活性。IL-15还诱导滑膜T细胞直接产生TNF-α。相反，IL-2在细胞接触依赖性或直接培养中诱导显著较低的TNF-α产生，并且IL-8和MIP-1 α无效。抗CD 69、LFA-1或ICAM-1的抗体显著抑制T细胞通过细胞接触激活巨噬细胞的能力。
Tumor necrosis factor-alpha occupies a central role in rheumatoid arthritis (RA) pathogenesis. We now report that interleukin-15 (IL-15) can induce TNF-alpha production in RA through activation of synovial T cells. Peripheral blood (PB) T cells activated by IL-15 induced significant TNF-alpha production by macrophages via a cell-contact-dependent mechanism. Freshly isolated RA synovial T cells possessed similar capability, and in vitro, IL-15 was necessary to maintain this activity. IL-15 also induced direct TNF-alpha production by synovial T cells. In contrast, IL-2 induced significantly lower TNF-alpha production in either cell-contact-dependent or direct culture, and IL-8 and MIP-1 alpha were ineffective. Antibodies against CD69, LFA-1 or ICAM-1 significantly inhibited the ability of T cells to activate macrophages by cell contact.