Mechanisms of dendritic cell-induced T cell proliferation in the primary MLR assay
Mechanisms of dendritic cell-induced T cell proliferation in the primary MLR assay
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DOI：
10.1016/s0165-2478(01)00235-8
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发表时间：
2001-09-03
影响因子：
4.4
通讯作者：
Shurin, GV
中科院分区：
文献类型：
--
作者：
Tourkova, IL;Yurkovetsky, ZR;Shurin, GV
DC 是独特的抗原呈递细胞，其在混合白细胞反应 (MLR) 测定中诱导 T 细胞增殖的能力通常用于评估其功能。为了确定初级 MLR 测定中 DC 诱导 T 细胞活化的机制，本研究检查了多种不同的试剂，这些试剂干扰细菌产物诱导的 DNA 合成、膜组织、蛋白质合成和成熟。虽然在 MLR 测定中只有活 DC 能够诱导 T 细胞增殖，但 DC 的照射并不影响它们的刺激能力。用多聚甲醛固定 DC 膜会导致 DC 诱导 T 细胞增殖的能力丧失，这表明质膜的物理组织在诱导 T 细胞活化中起着重要作用。此外，用放线菌酮预处理 DC 表明，蛋白质合成对于 DC 激活 T 细胞的能力并不重要。最后，金黄色葡萄球菌介导的 DC 激活显着增加了 T 细胞增殖，并且这种效应不依赖于 DC 的 IL-12 产生，因为 IL-12 敲除小鼠产生的 DC 与野生型 DC 没有不同。总之，这些数据表明 DC 膜结构负责抗原呈递和共刺激，并在 DC 识别和激活 T 细胞中发挥关键作用。 (C) 2001 Elsevier Science B.V. 保留所有权利。
DC are unique antigen presenting cells, and their ability to induce proliferation of T cells in a mixed leukocyte reaction (MLR) assay is commonly used for the evaluation of their function. To determine the mechanisms involved in DC-induced T cell activation in a primary MLR assay, a variety of different agents were examined in this study that interfere with DNA synthesis, membrane organization, protein synthesis, and maturation induced by bacterial products. While only live DC were able to induce T cell proliferation in the MLR assay, irradiation of DC did not influence their stimulatory capacity. Fixation of DC membrane with paraformaldehyde resulted in a loss of DC capacity to induce T cell proliferation demonstrating that physical organization of the plasma membranes plays an important role in the induction of T cell activation. In addition, the pretreatment of DC with cycloheximide revealed that protein synthesis was not critical for the ability of DC to activate T cells. Finally, Staphylococcus aureus-mediated activation of DC significantly increased T cell proliferation and this effect was not dependent on IL-12 production of DC since DC generated from IL-12 knockout mice were not different from wild type DC. In summary, these data suggest that DC membrane structures are responsible for the antigen presentation and co-stimulation and play a key role in T cell recognition and activation by DC. (C) 2001 Elsevier Science B.V. All rights reserved.