Specific niches for lung-resident memory CD8(+) T cells at the site of tissue regeneration enable CD69-independent maintenance

• Type of Material: Article
• Authors: Shiki Takamura, Kindai University; Hideki Yagi, Kindai University; Yoshiyuki Hakata, Kindai University; Chihiro Motozono, Kindai University; Sean R. McMaster, Emory University; Tomoko Masumoto, Kindai University; Makoto Fujisawa, Kindai University; Tomomi Chikaishi, Kindai University; Junko Komeda, Kindai University; Jun Itoh, Kindai University; Miki Umemura, Kindai University; Ami Kyusai, Kindai University; Michio Tomura, Osaka Otani University; Toshinori Nakayama, Chiba University; David L. Woodland, Keystone Symposia Molecular and Cellular Biology; Jacob Kohlmeier, Emory University; Masaaki Miyazawa, Kindai University
• Language: English
• Date: 2016-12-01
• Publisher: Rockefeller University
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Takamura et al.
• License: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1084/jem.20160938
• Title of Journal or Parent Work: Journal of Experimental Medicine
• Volume: 213
• Issue: 13
• Start Page: 3057
• End Page: 3073
• Grant/Funding Information: This work was supported by the Ministry of Education, Culture, Sports, Science and Technology with a Grant-in-Aid for Young Scientists ((A) 24689043 to S. Takamura) and a grant for Scientific Research on Innovative Areas (15H01268 to M. Miyazawa) and by the National Institutes of Health (grant R01HL122559 to J.E. Kohlmeier), Takeda Science Foundation (S. Takamura), Daiichi Sankyo Foundation of Life Science (S. Takamura), Uehara Memorial Foundation (S. Takamura), Kanae Foundation for the Promotion of Medical Science (S. Takamura), and Kindai University Anti-Aging Center (M. Miyazawa).
• Keywords: Research & Experimental Medicine; Life Sciences & Biomedicine; NONLYMPHOID TISSUE; RESPIRATORY VIRUS-INFECTIONS; INFLUENZA-VIRUS; AIRWAY STEM-CELLS; Science & Technology; RM CELLS; VIRAL-INFECTION; Immunology; RESIDUAL ANTIGEN; CUTTING EDGE; LYMPHOCYTE EGRESS; LOCAL ANTIGEN; Medicine, Research & Experimental
• Research Categories: Health Sciences, Immunology

Abstract

CD8+ tissue-resident memory T cells (TRM cells) reside permanently in nonlymphoid tissues and provide a first line of protection against invading pathogens. However, the precise localization of CD8+ TRM cells in the lung, which physiologically consists of a markedly scant interstitium compared with other mucosa, remains unclear. In this study, we show that lung CD8+ TRM cells localize predominantly in specific niches created at the site of regeneration after tissue injury, whereas peripheral tissuecirculating CD8+ effector memory T cells (TEM cells) are widely but sparsely distributed in unaffected areas. Although CD69 inhibited sphingosine 1-phosphate receptor 1-mediated egress of CD8+ T cells immediately after their recruitment into lung tissues, such inhibition was not required for the retention of cells in the TRM niches. Furthermore, despite rigid segregation of TEM cells from the TRM niche, prime-pull strategy with cognate antigen enabled the conversion from TEM cells to TRM cells by creating de novo TRM niches. Such damage site-specific localization of CD8+ TRM cells may be important for efficient protection against secondary infections by respiratory pathogens.