| Literature DB >> 30778243 |
Anthony W Purcell1, Katherine Kedzierska2, Marios Koutsakos3, Patricia T Illing1, Thi H O Nguyen3, Nicole A Mifsud1, Jeremy Chase Crawford4, Simone Rizzetto5, Auda A Eltahla5, E Bridie Clemens3, Sneha Sant3, Brendon Y Chua3,6, Chinn Yi Wong3, E Kaitlynn Allen4, Don Teng7, Pradyot Dash4, David F Boyd4, Ludivine Grzelak3,8, Weiguang Zeng3, Aeron C Hurt3,9, Ian Barr3,9,10, Steve Rockman3,11, David C Jackson3,6, Tom C Kotsimbos12,13, Allen C Cheng14,15, Michael Richards16, Glen P Westall17, Thomas Loudovaris18, Stuart I Mannering17, Michael Elliott19,20, Stuart G Tangye21,22, Linda M Wakim3, Jamie Rossjohn1,23,24, Dhanasekaran Vijaykrishna7, Fabio Luciani5, Paul G Thomas4, Stephanie Gras1,23.
Abstract
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, CD38+Ki67+CD8+ 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.Entities:
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Year: 2019 PMID： 30778243 DOI： 10.1038/s41590-019-0320-6
Source DB: PubMed Journal: Nat Immunol ISSN： 1529-2908 Impact factor: 25.606