Trudeau Institute, 154 Algonquin Avenue, Saranac Lake, NY 12983, USA.
Immunity. 2010 Jul 23;33(1):96-105. doi: 10.1016/j.immuni.2010.06.016.
Memory CD8(+) T cells in the lung airways provide protection from secondary respiratory virus challenge by limiting early viral replication. Here, we demonstrate that although airway-resident memory CD8(+) T cells were poorly cytolytic, memory CD8(+) T cells recruited to the airways early during a recall response showed markedly enhanced cytolytic ability. This enhanced lytic activity did not require cognate antigen stimulation, but rather was dependent on STAT1 transcription factor signaling through the interferon-alpha receptor (Ifnar1), resulting in the antigen-independent expression of granzyme B protein in both murine and human virus-specific T cells. Signaling through Ifnar1 was required for the enhanced lytic activity and control of early viral replication by memory CD8(+) T cells in the lung airways. These findings demonstrate that innate inflammatory signals act directly on memory T cells, enabling them to rapidly destroy infected host cells once they enter infected tissues.
肺气道中的记忆 CD8(+) T 细胞通过限制早期病毒复制为二次呼吸道病毒挑战提供保护。在这里，我们证明，尽管气道驻留记忆 CD8(+) T 细胞的细胞毒性较差，但在回忆反应早期募集到气道中的记忆 CD8(+) T 细胞表现出明显增强的细胞毒性能力。这种增强的裂解活性不需要同源抗原刺激，而是依赖于通过干扰素-α受体 (Ifnar1) 的 STAT1 转录因子信号传导，导致在小鼠和人类病毒特异性 T 细胞中抗原非依赖性表达颗粒酶 B 蛋白。Ifnar1 的信号传导对于肺气道中记忆 CD8(+) T 细胞的增强裂解活性和对早期病毒复制的控制是必需的。这些发现表明，先天炎症信号直接作用于记忆 T 细胞，使它们一旦进入感染组织，就能迅速破坏受感染的宿主细胞。
