Dendritic cells mediate NK cell help for Th1 and CTL responses: Two-signal requirement for the induction of NK cell helper function
Dendritic cells mediate NK cell help for Th1 and CTL responses: Two-signal requirement for the induction of NK cell helper function
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DOI：
10.4049/jimmunol.171.5.2366
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发表时间：
2003-09-01
影响因子：
4.4
通讯作者：
Kalinski, P
中科院分区：
文献类型：
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作者：
Mailliard, RB;Son, YI;Kalinski, P
病毒感染的早期阶段与树突状细胞（DC）和NK细胞的局部募集和活化相关。虽然已知活化的DC和NK细胞支持彼此的功能，但尚不清楚它们在感染组织中的局部相互作用是否可以调节随后迁移的DC诱导引流淋巴结中的T细胞应答的能力。在这项研究中，我们报告说，NK细胞能够诱导稳定的1型极化的“效应/记忆”DC（DC 1），作为载体的NK细胞衍生的辅助信号的发展1型免疫反应。NK细胞诱导的DC 1在随后的CD 40配体刺激后显示出强烈升高的产生IL-12 p70的能力。NK诱导的DC 1初始幼稚CD 4（+）Th细胞产生高水平的IFN-γ，但产生低水平的IL-4，并表现出强烈增强的诱导Ag特异性CD 8（+）T细胞应答的能力。静息NK细胞显示严格的激活要求，以执行这种新的DC介导的“辅助”功能。尽管它们与K562细胞的相互作用导致有效的靶细胞杀伤，但DO的诱导需要第二个NK细胞活化信号。这种共刺激信号可以由I型IFN提供，I型IFN是抗病毒应答的常见介质。因此，除了它们的细胞溶解功能之外，NK细胞还具有在更严格的条件下诱导的免疫调节活性。目前证明的NK细胞的辅助活性可能支持Th 1和CTL主导的1型免疫对细胞内病原体的发展，并可能对癌症免疫治疗有影响。
Early stages of viral infections are associated with local recruitment and activation of dendritic cells (DC) and NK cells. Although activated DC and NK cells are known to support each other's functions, it is less clear whether their local interaction in infected tissues can modulate the subsequent ability of migrating DC to induce T cell responses in draining lymph nodes. In this study, we report that NK cells are capable of inducing stable type 1-polarized "effector/memory" DC (DC1) that act as carriers of NK cell-derived helper signals for the development of type 1 immune responses. NK cell-induced DC1 show a strongly elevated ability to produce IL-12p70 after subsequent CD40 ligand stimulation. NK-induced DC1 prime naive CD4(+) Th cells for high levels of IFN-gamma, but low IL-4 production, and demonstrate a strongly enhanced ability to induce Ag-specific CD8(+) T cell responses. Resting NK cells display stringent activation requirements to perform this novel, DC-mediated, "helper" function. Although their interaction with K562 cells results in effective target cell killing, the induction of DO requires a second NK cell-activating signal. Such costimulatory signal can be provided by type I IFNs, common mediators of antiviral responses. Therefore, in addition to their cytolytic function, NK cells also have immunoregulatory activity, induced under more stringent conditions. The currently demonstrated helper activity of NK cells may support the development of Th1- and CTL-dominated type 1 immunity against intracellular pathogens and may have implications for cancer immunotherapy.