Albert Einstein College of Medicine, Department of Microbiology and Immunology, Bronx, NY 10461, USA.
Immunity. 2012 Sep 21;37(3):549-62. doi: 10.1016/j.immuni.2012.05.029. Epub 2012 Aug 30.
Memory CD8(+) T cells induced upon immunization exhibit improved functional features that contribute to protection of immunized hosts. Although both cognate antigen recognition and inflammation are important for memory CD8(+) T cell reactivation, the relative contribution of these factors and the cell types providing these signals in vivo are poorly defined. Here, we show that Ly6C(+)CCR2(+) inflammatory monocytes, a subset of monocytes, largely orchestrate memory CD8(+) T and NK lymphocytes activation by differentiating into interleukin-18 (IL-18)- and IL-15-producing cells in an inflammasome and type I interferon-IRF3-dependent manner. Memory CD8(+) T cells became potent effector cells by sensing inflammation from monocytes independently of their cognate antigen. Like NK cells, they underwent rapid mobilization, upregulated intense and sustained effector functions during bacterial, viral, and parasitic infections, and contributed to innate responses and protection in vivo. Thus, inflammatory monocyte-derived IL-18 and IL-15 are critical to initiate memory CD8(+) T and NK lymphocytes differentiation into antimicrobial effector cells.
免疫接种诱导的记忆 CD8(+)T 细胞表现出改善的功能特征，有助于保护免疫宿主。尽管同源抗原识别和炎症对于记忆 CD8(+)T 细胞的重新激活都很重要，但这些因素的相对贡献以及体内提供这些信号的细胞类型尚未得到明确界定。在这里，我们表明 Ly6C(+)CCR2(+)炎症性单核细胞，即单核细胞的一个子集，通过炎症小体和 I 型干扰素-IRF3 依赖性方式分化为产生白细胞介素-18 (IL-18)和 IL-15 的细胞，在很大程度上协调记忆 CD8(+)T 和 NK 淋巴细胞的激活。记忆 CD8(+)T 细胞通过独立于其同源抗原从单核细胞感知炎症而成为有效的效应细胞。与 NK 细胞一样，它们在细菌、病毒和寄生虫感染期间迅速动员，上调强烈和持续的效应功能，并有助于体内的先天反应和保护。因此，炎症性单核细胞衍生的 IL-18 和 IL-15 对于启动记忆 CD8(+)T 和 NK 淋巴细胞分化为抗微生物效应细胞至关重要。
