• Shiki Takamura, Hideki Yagi, Yoshiyuki Hakata, Chihiro Motozono, Sean R McMaster, Tomoko Masumoto, Makoto Fujisawa, Tomomi Chikaishi, Junko Komeda, Jun Itoh, Miki Umemura, Ami Kyusai, Michio Tomura, Toshinori Nakayama, David L Woodland, Jacob E Kohlmeier, and Masaaki Miyazawa.
• Department of Immunology, Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan takamura@med.kindai.ac.jp.
• J. Exp. Med. 2016 Dec 12; 213 (13): 3057-3073.

AbstractCD8+ 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 tissue-circulating 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.© 2016 Takamura et al.

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