ROLE OF THE CD40-CD40 LIGAND INTERACTION IN CD4(+) T-CELL CONTACT-DEPENDENT ACTIVATION OF MONOCYTE INTERLEUKIN-1 SYNTHESIS
ROLE OF THE CD40-CD40 LIGAND INTERACTION IN CD4(+) T-CELL CONTACT-DEPENDENT ACTIVATION OF MONOCYTE INTERLEUKIN-1 SYNTHESIS
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DOI：
10.1002/eji.1830241235
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发表时间：
1994-12-01
影响因子：
5.4
通讯作者：
SUTTLES, J
中科院分区：
文献类型：
--
作者：
WAGNER, DH;STOUT, RD;SUTTLES, J
大多数诱导单核细胞中细胞因子合成的研究都采用了外源性触发剂，如脂多糖。然而，在非脓毒性炎症反应（如类风湿性关节炎）中，单核细胞活化是T细胞产生信号的结果。在以前的报告中，我们和其他人已经证明了接触依赖性T细胞产生的信号能够促进巨噬细胞活化。我们已经证明，在没有共刺激细胞因子的情况下，来自抗CD3活化的纯化的外周CD4（+）T细胞（Tm-A）的质膜而不是来自静息的CD4（+）细胞（Tm-R）的质膜诱导单核细胞合成白细胞介素（IL）-1。确定活化的CD4（+）T细胞所特有的分子表达动力学的研究表明，活化后6小时出现最佳表达，所述活化的CD4（+）T细胞与单核细胞相互作用以诱导IL-1。这与先前报道的活化的外周T细胞上的CD40配体（CD40L）表达的动力学相匹配，暗示CD40-CD40L相互作用是IL-1信号传导事件的起始者的候选者。Tm-A诱导静息单核细胞IL-1合成的能力可通过添加单克隆抗CD40 L抗体5c8而显著降低。此外，单克隆抗CD40 IgM（BL-C4）证明其诱导静息单核细胞合成IL-1的能力是显著的。总之，这些结果表明，CD40-CD40L相互作用提供了CD4（+）T细胞接触依赖性激活单核细胞IL-1合成的关键组成部分。
Most studies of the induction of cytokine synthesis in monocytes have employed an exogenous triggering agent such as lipopolysaccharide. However, in nonseptic inflammatory responses (e.g. rheumatoid arthritis) monocyte activation occurs as a result of T cell-generated signals. In previous reports, we and others have demonstrated that contact-dependent T cell-generated signals are capable of contributing to macrophage activation. We have shown that plasma membranes from anti-CD3 activated purified peripheral CD4(+) T cells (Tm-A) but not from resting CD4(+) cells (Tm-R) induce monocytes to synthesize interleukin (IL)-1 in the absence of co-stimulatory cytokines. Studies to determine the expression kinetics of the molecule(s) unique to activated CD4(+) T cells which interact with monocytes to induce IL-1 revealed that optimal expression occurred at 6 h post activation. This matched the previously reported kinetics of expression of CD40 ligand (CD40L) on activated peripheral T cells, implicating the CD40-CD40L interaction as a candidate for the initiator of the IL-1 signaling event. The ability of Tm-A to induce IL-1 synthesis in resting monocytes could be markedly reduced by addition of a monoclonal anti-CD40L antibody, 5c8. In addition, a monoclonal anti-CD40 IgM (BL-C4) proved dramatic in its ability to induce resting monocytes to synthesize IL-1. In summary, these results demonstrate that the CD40-CD40L interaction provides a critical component of CD4(+) T cell contact-dependent activation of monocyte IL-1 synthesis.