The role of monocytes in human lymphocyte activation by mitogens.
The role of monocytes in human lymphocyte activation by mitogens.
复制标题
单核细胞在有丝分裂原激活人淋巴细胞中的作用。
作者：
J. D. de Vries;A. Caviles;W. S. Bont;J. Mendelsohn
进行研究以确定单核细胞在促细胞分裂剂激活人类淋巴细胞中的作用。在新装置中以 1 x G 速度沉降，以获得几乎不含单核细胞的高度纯化的淋巴细胞级分 (LF)（0.02 至 0.4%）和富含单核细胞的级分（MF）（64 至 92%）。淋巴细胞组分对植物血凝素、刀豆球蛋白 A 和美洲商陆有丝分裂原的平均峰值反应分别是含有约 20% 单核细胞的未分级淋巴细胞培养物所达到的反应的 19%、10% 和 9%。这些变化并非归因于剂量要求的改变。当使用丝裂霉素-C 处理的 MF 细胞重建 LF 培养物时，发现 4% 的单核细胞完全恢复对植物血凝素的反应，而需要 8% 至 16% 的单核细胞才能对其他丝裂原产生正常反应。更多数量的 MF 细胞产生超常反应，其中 35% 至 50% 的单核细胞产生最佳刺激。同种异体单核细胞能够完全重建 LF 的反应，而 2-巯基乙醇 (50 µM) 仅具有轻微效果。在探索单核细胞增强淋巴细胞有丝分裂活性的可能机制时，发现 MF 培养物的上清液可以部分但不完全重建 LF 反应，这表明可能需要与 MF 接触才能获得最佳效果。在 LF 中添加分级数量的单核细胞会改变反应动力学和增殖峰值水平。单核细胞耗竭还导致培养的未刺激 LF 的存活率显着降低。这些观察结果表明，单核细胞在增强促有丝分裂反应方面可能具有多种作用，包括接触介导的与淋巴细胞的相互作用（可能以最佳方式呈现有丝分裂原）；增强增殖动力学和响应亚群的大小，并维持培养物中必需的生长因子。因此，培养的淋巴细胞制剂中单核细胞含量的微小差异可能是许多经常观察到的有丝分裂原反应性变化的原因。
Studies were performed to determine the role of monocytes in human lymphocyte activation by mitogens. Velocity sedimentation at 1 x G in a new apparatus was utilized to obtain highly purified lymphocyte fractions (LF) nearly free of monocytes (0.02 to 0.4%) and a fraction (MF) enriched for monocytes (64 to 92%). The average peak responses of the lymphocyte fractions to phytohemagglutinin, concanavalin A, and pokeweed mitogen were 19, 10, and 9% of the responses achieved with unfractionated lymphocyte cultures containing approximately 20% monocytes. These changes were not attributable to altered dose requirements. When mitomycin-C-treated MF cells were used to reconstitute LF cultures, it was found that 4% monocytes fully restored the response to phytohemagglutinin whereas 8 to 16% monocytes were required for a normal response to the other mitogens. Higher numbers of MF cells produced supranormal responses, with 35 to 50% monocytes resulting in the optimal stimulation. Allogeneic monocytes were able to fully reconstitute the response of LF, and 2-mercaptoethanol (50 microM) was only slightly effective. In exploring possible mechanisms by which monocytes potentiate the mitogenic activity of lymphocytes, it was found that the supernatants of MF cultures could partially, but not completely, reconstitute LF responses, suggesting that contact with MF may be required for optimal effectiveness. Addition of graded numbers of monocytes to LF altered both the kinetics of the response and the peak level of proliferation. Monocyte depletion also resulted in markedly decreased survival of cultured unstimulated LF. These observations suggest a variety of possible effects of monocytes in potentiating mitogenic responses, including contact-mediated interactions with lymphocytes (possibly to present the mitogen optimally); enhancement of proliferation kinetics and the size of the responding subpopulation, and maintenance of a requisite growth factor(s) in the culture. Small differences in the monocyte content of cultured lymphocyte preparations may thus account for many of the often observed variations in mitogen responsiveness.