首页> 外文期刊>Journal of Immunological Methods >Comparative analysis of lymphocyte activation marker expression and cytokine secretion profile in stimulated human peripheral blood mononuclear cell cultures: an in vitro model to monitor cellular immune function.
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Comparative analysis of lymphocyte activation marker expression and cytokine secretion profile in stimulated human peripheral blood mononuclear cell cultures: an in vitro model to monitor cellular immune function.

机译:刺激的人外周血单个核细胞培养物中淋巴细胞活化标志物表达和细胞因子分泌谱的比较分析:监测细胞免疫功能的体外模型。

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摘要

Activation of lymphocytes is a complex, yet finely regulated cascade of events that results in the expression of cytokine receptors, production and secretion of cytokines and expression of several cell surface molecules that eventually lead to divergent immune responses. Assessing the qualitative and quantitative nature of lymphocyte function following immunotherapy provides valuable information about the immune responses mediated by a therapeutic agent. To facilitate evaluation of the immunomodulatory activity of therapeutic agents, we have established a platform of in vitro immunoassays with normal human peripheral blood mononuclear cells (PBMCs) treated with several polyclonal activators that are known to exhibit different modes of action. We evaluated the kinetics of cell surface marker expression and cytokine release from PBMCs stimulated in parallel with various activating agents over a time course. These stimulating agents induced early (CD69 and CD71) and late (CD25 and HLA-DR) activation markers to varying antigen densities, indicated different cytokine profiles, and showed differential inhibition with dexamethasone (DEX), an inhibitor of early signaling events. Based on the association or correlation of the kinetics of activation marker expression and secreted cytokines, the results of our study indicate the appropriate time points for the simultaneous measurement of both these activation products. This study defines the kinetics for both measures of T cell activation and provides a comprehensive review with various polyclonal activators that can serve as a reference for monitoring lymphocyte function in clinical study samples.
机译:淋巴细胞的激活是一个复杂但调控良好的事件级联反应,可导致细胞因子受体的表达,细胞因子的产生和分泌以及几种细胞表面分子的表达,最终导致发散的免疫反应。评估免疫疗法后淋巴细胞功能的定性和定量性质,可提供有关由治疗剂介导的免疫反应的宝贵信息。为了促进对治疗剂免疫调节活性的评估,我们建立了一个体外免疫测定平台,该平台上的人体正常外周血单个核细胞(PBMC)已用几种已知表现出不同作用方式的多克隆激活剂处理过。我们评估了在一段时间内,与各种活化剂平行刺激的PBMC中细胞表面标志物表达和细胞因子释放的动力学。这些刺激剂诱导早期(CD69和CD71)和晚期(CD25和HLA-DR)活化标记物改变抗原密度,指示不同的细胞因子谱,并显示地塞米松(DEX)(早期信号事件的抑制剂)具有不同的抑制作用。基于激活标记物表达和分泌的细胞因子动力学的关联或相关性,我们的研究结果表明了同时测量这两种激活产物的合适时间点。这项研究定义了T细胞活化的两种动力学,并提供了多种多克隆活化剂的全面综述,可以作为监测临床研究样品中淋巴细胞功能的参考。

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