Functional interactions of T cells with endothelial cells: the role of CD40L-CD40-mediated signals.
Functional interactions of T cells with endothelial cells: the role of CD40L-CD40-mediated signals.
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DOI：
10.1084/jem.182.6.1857
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发表时间：
1995-12-01
期刊：
影响因子：
--
通讯作者：
Chess L
中科院分区：
文献类型：
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作者：
Yellin MJ;Brett J;Baum D;Matsushima A;Szabolcs M;Stern D;Chess L
CD40在多种细胞上表达，包括B细胞、单核细胞、树突状细胞和成纤维细胞。CD40与CD40L相互作用，CD40L是一种30-33-kD激活诱导的CD4+ T细胞表面分子。已知CD40L-CD40相互作用在体外和体内B细胞活化和分化中起关键作用。我们现在报道正常的人内皮细胞也在原位表达CD40，并且CD40L-CD40相互作用诱导内皮细胞在体外活化。免疫组织化学检测正常脾脏、甲状腺、皮肤、肌肉、肾脏、肺或脐带的冷冻切片CD40的表达。所有组织的内皮细胞原位表达CD40。此外，人脐静脉内皮细胞（HUVEC）在体外表达CD40，重组干扰素γ诱导HUVEC CD40上调。CD40在HUVEC上的表达在功能上是显著的，因为CD40L+ Jurkat T细胞或CD40L+ 293肾细胞转染，而不是对照细胞，在体外上调HUVEC CD54（细胞间粘附分子-1）、CD62E （e-选择素）和CD106（血管细胞粘附分子-1）的表达。此外，CD40L-、白细胞介素1-或肿瘤坏死因子α -诱导的CD54、CD62E和CD106对HUVEC的上调动力学是相似的。最后，CD40L-CD40相互作用不会诱导体外HUVEC上CD80、CD86或主要组织相容性复合体II类的表达。这些结果表明，CD40L-CD40相互作用诱导内皮细胞在体外活化。此外，他们提出了激活的CD4+ T细胞可能通过上调内皮细胞表面粘附分子的表达来增强体内炎症反应的机制。
CD40 is expressed on a variety of cells, including B cells, monocytes, dendritic cells, and fibroblasts. CD40 interacts with CD40L, a 30-33-kD activation-induced CD4+ T cell surface molecule. CD40L-CD40 interactions are known to play key roles in B cell activation and differentiation in vitro and in vivo. We now report that normal human endothelial cells also express CD40 in situ, and CD40L-CD40 interactions induce endothelial cell activation in vitro. Frozen sections from normal spleen, thyroid, skin, muscle, kidney, lung, or umbilical cord were studied for CD40 expression by immunohistochemistry. Endothelial cells from all tissues studied express CD40 in situ. Moreover, human umbilical vein endothelial cells (HUVEC) express CD40 in vitro, and recombinant interferon gamma induces HUVEC CD40 upregulation. CD40 expression on HUVEC is functionally significant because CD40L+ Jurkat T cells or CD40L+ 293 kidney cell transfectants, but not control cells, upregulate HUVEC CD54 (intercellular adhesion molecule-1), CD62E (E-selectin), and CD106 (vascular cell adhesion molecule-1) expression in vitro. Moreover, the kinetics of CD40L-, interleukin 1-, or tumor necrosis factor alpha- induced CD54, CD62E, and CD106 upregulation on HUVEC are similar. Finally, CD40L-CD40 interactions do not induce CD80, CD86, or major histocompatibility complex class II expression on HUVEC in vitro. These results demonstrate that CD40L-CD40 interactions induce endothelial cell activation in vitro. Moreover, they suggest a mechanism by which activated CD4+ T cells may augment inflammatory responses in vivo by upregulating the expression of endothelial cell surface adhesion molecules.