Böttcher Jan P, Schanz Oliver, Garbers Christoph, Zaremba Anne, Hegenbarth Silke, Kurts Christian, Beyer Marc, Schultze Joachim L, Kastenmüller Wolfgang, Rose-John Stefan, Knolle Percy A
Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Bonn 53105, Germany.
Institute of Biochemistry, Universität Kiel, Kiel 24098, Germany.
Cell Rep. 2014 Sep 11;8(5):1318-27. doi: 10.1016/j.celrep.2014.07.008. Epub 2014 Sep 4.
Immune control of infections with viruses or intracellular bacteria relies on cytotoxic CD8(+) T cells that use granzyme B (GzmB) for elimination of infected cells. During inflammation, mature antigen-presenting dendritic cells instruct naive T cells within lymphoid organs to develop into effector T cells. Here, we report a mechanistically distinct and more rapid process of effector T cell development occurring within 18 hr. Such rapid acquisition of effector T cell function occurred through cross-presenting liver sinusoidal endothelial cells (LSECs) in the absence of innate immune stimulation and known costimulatory signaling. Rather, interleukin-6 (IL-6) trans-signaling was required and sufficient for rapid induction of GzmB expression in CD8(+) T cells. Such LSEC-stimulated GzmB-expressing CD8(+) T cells further responded to inflammatory cytokines, eliciting increased and protracted effector functions. Our findings identify a role for IL-6 trans-signaling in rapid generation of effector function in CD8(+) T cells that may be beneficial for vaccination strategies.
对病毒或细胞内细菌感染的免疫控制依赖于细胞毒性CD8(+) T细胞，这些细胞利用颗粒酶B（GzmB）来清除被感染的细胞。在炎症过程中，成熟的抗原呈递树突状细胞指导淋巴器官内的幼稚T细胞发育成效应T细胞。在此，我们报告了一个在18小时内发生的、机制上不同且更快的效应T细胞发育过程。效应T细胞功能的这种快速获得是通过在没有先天免疫刺激和已知共刺激信号的情况下交叉呈递肝窦内皮细胞（LSEC）实现的。相反，白细胞介素-6（IL-6）转信号传导对于在CD8(+) T细胞中快速诱导GzmB表达是必需且足够的。这种LSEC刺激的表达GzmB的CD8(+) T细胞进一步对炎性细胞因子作出反应，引发增强且持久的效应功能。我们的研究结果确定了IL-6转信号传导在CD8(+) T细胞效应功能快速产生中的作用，这可能对疫苗接种策略有益。
