Peng X, Kasran A, Warmerdam P A, de Boer M, Ceuppens J L
Department of Pathophysiology, Catholic University of Leuven, Belgium.
Eur J Immunol. 1996 Jul;26(7):1621-7. doi: 10.1002/eji.1830260732.
The interaction of CD40 ligand (CD40L) on activated T cells with CD40 on B cells, monocytes and dendritic cells is essential for humoral immunity and for up-regulation of antigen-presenting cell (APC) functions, as a result of signaling through CD40. There are also some indications that after interaction with CD40, CD40L can directly signal T cells. In this study we demonstrate that upon stimulation of human peripheral blood T cells through the T cell receptor (TCR)/CD3 complex, CD40/CD40L interaction strongly enhances the production of Th1 cytokines such as interleukin (IL)-2 and interferon (IFN)-gamma and Th2 cytokines such as IL-4, IL-5 and IL-10 by a direct effect on T cells. Furthermore, CD40/CD40L interaction synergizes with IL-12 in selectively enhancing IFN-gamma production by purified anti-CD3-stimulated T cells. These effects were observed at both the protein and the mRNA level. Both CD4+ and CD8+ T cells were able to produce IFN-gamma in the presence of helper signals from IL-12 and CD40, although CD8+ T cells were less active. Since CD40/CD40L interaction also up-regulates IL-12 production and B7 expression by APC, our results suggest that CD40/CD40L interaction is bidirectional, and promotes activation of both APC and T cells.
活化T细胞上的CD40配体（CD40L）与B细胞、单核细胞和树突状细胞上的CD40相互作用，对于体液免疫以及上调抗原呈递细胞（APC）的功能至关重要，这是通过CD40信号传导的结果。也有一些迹象表明，与CD40相互作用后，CD40L可直接向T细胞发出信号。在本研究中，我们证明，通过T细胞受体（TCR）/CD3复合物刺激人外周血T细胞时，CD40/CD40L相互作用通过对T细胞的直接作用，强烈增强Th1细胞因子如白细胞介素（IL）-2和干扰素（IFN）-γ以及Th2细胞因子如IL-4、IL-5和IL-10的产生。此外，CD40/CD40L相互作用与IL-12协同作用，选择性增强纯化的抗CD3刺激的T细胞产生IFN-γ。在蛋白质和mRNA水平均观察到这些效应。在来自IL-12和CD40的辅助信号存在下，CD4+和CD8+T细胞均能够产生IFN-γ，尽管CD8+T细胞活性较低。由于CD40/CD40L相互作用还上调APC产生IL-12和表达B7，我们的结果表明CD40/CD40L相互作用是双向的，并促进APC和T细胞的活化。
