Böttcher Jan P, Beyer Marc, Meissner Felix, Abdullah Zeinab, Sander Jil, Höchst Bastian, Eickhoff Sarah, Rieckmann Jan C, Russo Caroline, Bauer Tanja, Flecken Tobias, Giesen Dominik, Engel Daniel, Jung Steffen, Busch Dirk H, Protzer Ulrike, Thimme Robert, Mann Matthias, Kurts Christian, Schultze Joachim L, Kastenmüller Wolfgang, Knolle Percy A
Institute of Experimental Immunology, Universitätsklinikum Bonn, Sigmund-Freud-Street 25, Bonn 53105, Germany.
Genomics and Immunoregulation, LIMES-Institute, Universität Bonn, Carl-Troll-Street 31, Bonn 53115, Germany.
Nat Commun. 2015 Sep 25;6:8306. doi: 10.1038/ncomms9306.
Localization of memory CD8(+) T cells to lymphoid or peripheral tissues is believed to correlate with proliferative capacity or effector function. Here we demonstrate that the fractalkine-receptor/CX3CR1 distinguishes memory CD8(+) T cells with cytotoxic effector function from those with proliferative capacity, independent of tissue-homing properties. CX3CR1-based transcriptome and proteome-profiling defines a core signature of memory CD8(+) T cells with effector function. We find CD62L(hi)CX3CR1(+) memory T cells that reside within lymph nodes. This population shows distinct migration patterns and positioning in proximity to pathogen entry sites. Virus-specific CX3CR1(+) memory CD8(+) T cells are scarce during chronic infection in humans and mice but increase when infection is controlled spontaneously or by therapeutic intervention. This CX3CR1-based functional classification will help to resolve the principles of protective CD8(+) T-cell memory.
记忆性CD8(+) T细胞定位于淋巴组织或外周组织被认为与增殖能力或效应功能相关。在此，我们证明趋化因子受体/CX3CR1可区分具有细胞毒性效应功能的记忆性CD8(+) T细胞和具有增殖能力的记忆性CD8(+) T细胞，这与组织归巢特性无关。基于CX3CR1的转录组和蛋白质组分析确定了具有效应功能的记忆性CD8(+) T细胞的核心特征。我们发现存在于淋巴结内的CD62L(hi)CX3CR1(+)记忆性T细胞。这群细胞表现出独特的迁移模式，并定位在病原体进入部位附近。在人类和小鼠的慢性感染期间，病毒特异性CX3CR1(+)记忆性CD8(+) T细胞稀少，但在感染被自发控制或通过治疗干预后会增加。这种基于CX3CR1的功能分类将有助于阐明保护性CD8(+) T细胞记忆的原理。
