Pulmonary antigen encounter regulates the establishment of tissue-resident CD8 memory T cells in the lung airways and parenchyma

• Type of Material: Article
• Authors: Sean R. McMaster, Emory University; Alexander N. Wein, Emory University; Paul R. Dunbar, Emory University; Sarah L. Hayward, Emory University; Emily K. Cartwright, Emory University; Timothy L. Denning, Georgia State University; Jacob Kohlmeier, Emory University
• Language: English
• Date: 2018-07-01
• Publisher: Springer Nature [academic journals on nature.com]: Hybrid Journals
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Society for Mucosal Immunology.
• Final Published Version (URL): http://dx.doi.org/10.1038/s41385-018-0003-x
• Title of Journal or Parent Work: Mucosal Immunology
• ISSN: 1933-0219
• Volume: 11
• Issue: 4
• Start Page: 1071
• End Page: 1078
• Grant/Funding Information: This work was supported by National Institutes of Health grant HL122559 (to J.E.K.) and Centers of Excellence in Influenza Research and Surveillance Contract HHSN272201400004C (to J.E.K.). S.R.M. was supported by National Institutes of Health Grants F30 HL118954 and T32 AI007610.; P.R.D. was supported by National Institutes of Health Grant F31 AI124611.
• Keywords: NONLYMPHOID TISSUE; VIRUS; INFECTION; LOCAL ANTIGEN; PANDEMIC INFLUENZA; EFFECTOR; Science & Technology; MAINTENANCE; Immunology; MIGRATION; Life Sciences & Biomedicine; PROTECTION; DIFFERENTIATION
• Research Categories: Health Sciences, Immunology; Health Sciences, Medicine and Surgery

Abstract

Resident memory CD8 T (TRM) cells in the lung parenchyma (LP) and airways provide heterologous protection against influenza virus challenge. However, scant knowledge exists regarding factors necessary to establish and maintain lung CD8 TRM. Here we demonstrate that, in contrast to mechanisms described for other tissues, airway, and LP CD8 TRMestablishment requires cognate antigen recognition in the lung. Systemic effector CD8 T cells could be transiently pulled into the lung in response to localized inflammation, however these effector cells failed to establish tissue residency unless antigen was present in the pulmonary environment. The interaction of effector CD8 T cells with cognate antigen in the lung resulted in increased and prolonged expression of the tissue-retention markers CD69 and CD103, and increased expression of the adhesion molecule VLA-1. The inability of localized inflammation alone to establish lung TRMresulted in decreased viral clearance and increased mortality following heterosubtypic influenza challenge, despite equal numbers of circulating memory CD8 T cells. These findings demonstrate that pulmonary antigen encounter is required for the establishment of lung CD8 TRMand may inform future vaccine strategies to generate robust cellular immunity against respiratory pathogens.