Interleukin 15 is produced by endothelial cells and increases the transendothelial migration of T cells in vitro and in the SCID mouse-human rheumatoid arthritis model in vivo

Interleukin 15 is produced by endothelial cells and increases the transendothelial migration of T cells in vitro and in the SCID mouse-human rheumatoid arthritis model in vivo
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DOI:
10.1172/jci1986
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发表时间:
1998-03-15
影响因子:
15.9
通讯作者:
Lipsky, PE
Lipsky, PE
中科院分区:
医学1区
文献类型:
--
作者:
Oppenheimer-Marks, N;Brezinschek, RI;Lipsky, PE

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研究了内皮细胞(EC)产生IL-15的能力以及IL-15影响T细胞跨内皮迁移的能力。人脐静脉内皮细胞同时表达IL-15 mRNA和蛋白。此外,内皮来源的IL-15增强了T细胞的跨内皮迁移,这可以通过阻断IL-15单克隆抗体来抑制这一过程。IL-15通过激活整合素粘附分子LFA-1 (CD11a/CD18)的结合能力增强T细胞的跨内皮迁移,并增加T细胞的运动性。此外,IL-15诱导早期活化分子CD69的表达。IL-15在体内调节T细胞迁移中的重要性被证明是通过其在移植到免疫缺陷SCID小鼠的类风湿关节炎滑膜组织中增强过继转移的人类T细胞积累的能力。这些结果表明EC产生IL-15,并暗示内皮IL-15在刺激T细胞外渗到炎症组织中起关键作用。
The capacity of endothelial cells (EC) to produce IL-15 and the capacity of IL-15 to influence transendothelial migration of T cells was examined. Human umbilical vein endothelial cells expressed both IL-15 mRNA and protein. Moreover, endothelial-derived IL-15 enhanced transendothelial migration of T cells as evidenced by the inhibition of this process by blocking monoclonal antibodies to IL-15. IL-15 enhanced transendothelial migration of T cells by activating the binding capacity of the integrin adhesion molecule LFA-1 (CD11a/CD18) and also increased T cell motility. In addition, IL-15 induced expression of the early activation molecule CD69. The importance of IL-15 in regulating migration of T cells in vivo was documented by its capacity to enhance accumulation of adoptively transferred human T cells in rheumatoid arthritis synovial tissue engrafted into immune deficient SCID mice. These results demonstrate that EC produce IL-15 and imply that endothelial IL-15 plays a critical role in stimulation of T cells to extravasate into inflammatory tissue.