Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Immunity. 2013 Nov 14;39(5):939-48. doi: 10.1016/j.immuni.2013.09.013.
Inducing memory CD8(+) T cells specific for conserved antigens from influenza A virus (IAV) is a potential strategy for broadly protective vaccines. Here we show that memory CD8(+) T cells in the airways played an important role in early control of IAV. Expression of the chemokine receptor CXCR3 was critical for memory CD8(+) T cells to populate the airways during the steady state and vaccination approaches were designed to favor the establishment of memory CD8(+) T cells in the airways. Specifically, we found that interleukin-12 (IL-12) signaling shortly after immunization limited CXCR3 expression on memory CD8(+) T cells. Neutralization of IL-12 or adjuvants that did not induce high amounts of IL-12 enhanced CXCR3 expression, sustained airway localization of memory CD8(+) T cells, and resulted in superior protection against IAV.
诱导针对流感病毒 (IAV) 保守抗原的记忆 CD8(+) T 细胞是一种具有广泛保护作用的疫苗的潜在策略。在这里，我们表明气道中的记忆 CD8(+) T 细胞在早期控制 IAV 方面发挥了重要作用。趋化因子受体 CXCR3 的表达对于记忆 CD8(+) T 细胞在稳态和疫苗接种期间在气道中定殖至关重要，设计了疫苗接种方法来有利于记忆 CD8(+) T 细胞在气道中的建立。具体来说，我们发现免疫后不久白细胞介素 12 (IL-12) 信号转导会限制记忆 CD8(+) T 细胞上 CXCR3 的表达。中和 IL-12 或不诱导大量 IL-12 的佐剂增强了 CXCR3 的表达，维持了记忆 CD8(+) T 细胞在气道中的定位，并导致对 IAV 的更好保护。
