Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia.
Infection and Immunity Program & Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Nat Immunol. 2019 May;20(5):613-625. doi: 10.1038/s41590-019-0320-6. Epub 2019 Feb 18.
Influenza A, B and C viruses (IAV, IBV and ICV, respectively) circulate globally and infect humans, with IAV and IBV causing the most severe disease. CD8 T cells confer cross-protection against IAV strains, however the responses of CD8 T cells to IBV and ICV are understudied. We investigated the breadth of CD8 T cell cross-recognition and provide evidence of CD8 T cell cross-reactivity across IAV, IBV and ICV. We identified immunodominant CD8 T cell epitopes from IBVs that were protective in mice and found memory CD8 T cells directed against universal and influenza-virus-type-specific epitopes in the blood and lungs of healthy humans. Lung-derived CD8 T cells displayed tissue-resident memory phenotypes. Notably, CD38Ki67CD8 effector T cells directed against novel epitopes were readily detected in IAV- or IBV-infected pediatric and adult subjects. Our study introduces a new paradigm whereby CD8 T cells confer unprecedented cross-reactivity across all influenza viruses, a key finding for the design of universal vaccines.
甲型、乙型和丙型流感病毒（分别为 IAV、IBV 和 ICV）在全球范围内传播并感染人类，其中 IAV 和 IBV 可导致最严重的疾病。CD8 T 细胞可提供针对 IAV 株的交叉保护，但 CD8 T 细胞对 IBV 和 ICV 的反应尚未得到充分研究。我们研究了 CD8 T 细胞交叉识别的广度，并提供了 IAV、IBV 和 ICV 之间 CD8 T 细胞交叉反应性的证据。我们从 IBV 中鉴定出了保护性的免疫优势 CD8 T 细胞表位，并在健康人类的血液和肺部中发现了针对通用和流感病毒特异性表位的记忆 CD8 T 细胞。肺来源的 CD8 T 细胞显示出组织驻留记忆表型。值得注意的是，针对新型表位的 CD38Ki67CD8 效应 T 细胞在 IAV 或 IBV 感染的儿科和成年患者中很容易被检测到。我们的研究引入了一个新的范例，即 CD8 T 细胞在所有流感病毒之间提供前所未有的交叉反应性，这是通用疫苗设计的关键发现。
