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树突状细胞(DC)促进自然杀伤(NK)细胞功能:人类DC/NK细胞相互作用的动态变化

Dendritic cells (DC) promote natural killer (NK) cell functions: dynamics of the human DC/NK cell cross talk.

作者信息

Fernandez Nadine C, Flament Caroline, Crépineau Florent, Angevin Eric, Vivier Eric, Zitvogel Laurence

机构信息

Unité d'Immunologie, Département de Biologie Clinique, Institut Gustave-Roussy, 39, rue Camille-Desmoulins, 94805 Villejuif Cedex, France.

出版信息

Eur Cytokine Netw. 2002 Jan-Mar;13(1):17-27.

Abstract

Dendritic cells (DC) were originally found critical in the setting of cognate immune responses. We first demonstrated that DC can also induce mouse NK cell activation and NK cell dependent-antitumor effects in mice. Here we analyzed the dynamics between DC and NK cells in human in vitro model systems. In the absence of LPS, DC do not trigger resting NK cells. Conversely, in the presence of LPS, resting bulk NK cells interacting with DC acquire CD25 and CD69 surface expression, produce high levels of IFN-gamma and lyse DAUDI cells. On activated IL-2 dependent NK cell lines, regardless of their differentiation stage, DC maintain or enhance NK cell proliferation and effector functions in the absence of exogenous cytokines. While IL-12, IL-15 and IL-18 are not critical, a direct cell-to-cell contact is mandatory for NK activation by DC and required for optimal proliferation. These data imply that DC also modulate human NK cell innate effector functions.

摘要

树突状细胞(DC)最初被发现对同源免疫反应的发生至关重要。我们首先证明DC在小鼠中也能诱导小鼠自然杀伤细胞(NK细胞)活化以及NK细胞依赖性抗肿瘤效应。在此,我们在人源体外模型系统中分析了DC与NK细胞之间的动态关系。在没有脂多糖(LPS)的情况下,DC不会触发静息NK细胞。相反,在有LPS存在时,与DC相互作用的静息NK细胞群体获得CD25和CD69表面表达,产生高水平的γ干扰素并裂解DAUDI细胞。在活化的白细胞介素-2(IL-2)依赖性NK细胞系中,无论其分化阶段如何,在没有外源性细胞因子的情况下,DC维持或增强NK细胞增殖及效应功能。虽然IL-12、IL-15和IL-18并非关键因素,但DC激活NK细胞需要细胞间直接接触,且这是最佳增殖所必需的。这些数据表明DC也调节人NK细胞的固有效应功能。

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