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
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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DOI：
10.1016/j.jim.2004.07.006
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发表时间：
2004-10-01
影响因子：
2.2
通讯作者：
Prabhakar, U
中科院分区：
文献类型：
--
作者：
Reddy, M;Eirikis, E;Prabhakar, U
淋巴细胞的活化是一个复杂但精细调节的级联事件，其导致细胞因子受体的表达、细胞因子的产生和分泌以及最终导致不同免疫应答的几种细胞表面分子的表达。评估免疫治疗后淋巴细胞功能的定性和定量性质提供了有关治疗剂介导的免疫应答的有价值的信息。为了便于评价治疗药物的免疫调节活性，我们建立了一个用几种已知表现出不同作用模式的多克隆活化剂处理的正常人外周血单核细胞（PBMC）进行体外免疫测定的平台。我们评估了细胞表面标志物表达的动力学和细胞因子从PBMC中释放，这些PBMC在一段时间内与各种活化剂平行刺激。这些刺激剂诱导早期（CD 69和CD 71）和晚期（CD 25和HLA-DR）活化标志物不同的抗原密度，表明不同的细胞因子谱，并显示与地塞米松（DEX），早期信号传导事件的抑制剂的差异抑制。基于活化标志物表达和分泌的细胞因子的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活化产物的适当时间点。本研究定义了T细胞活化的两种措施的动力学，并提供了一个全面的审查与各种多克隆活化剂，可以作为一个参考监测淋巴细胞功能的临床研究样本。(C)2004 Elsevier B. V.保留所有权利。
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. (C) 2004 Elsevier B.V. All rights reserved.