Specific niches for lung-resident memory CD8+ T cells at the site of tissue regeneration enable CD69-independent maintenance.
CD8+tissue-resident memory T cells (TRMcells) reside permanently in nonlymphoid tissues and provide a first line of protection against invading pathogens. However, the precise localization of CD8+TRMcells 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+TRMcells localize predominantly in specific niches created at the site of regeneration after tissue injury, whereas peripheral tissue-circulating CD8+effector memory T cells (TEMcells) 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 TRMniches. Furthermore, despite rigid segregation of TEMcells from the TRMniche, prime-pull strategy with cognate antigen enabled the conversion from TEMcells to TRMcells by creating de novo TRMniches. Such damage site-specific localization of CD8+TRMcells may be important for efficient protection against secondary infections by respiratory pathogens.
Department of Immunology, Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan takamura@med.kindai.ac.jp.
Shiki
0000-0001-6681-0258
S
Takamura
Cell Biology Laboratory, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan.
Hideki
0000-0002-1550-029X
H
Yagi
Department of Immunology, Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan.
Yoshiyuki
Y
Hakata
Department of Immunology, Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan.
Chihiro
C
Motozono
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.
Sean R
SR
McMaster
Department of Immunology, Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan.
Tomoko
T
Masumoto
Department of Immunology, Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan.
Makoto
M
Fujisawa
Department of Immunology, Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan.
Tomomi
T
Chikaishi
Cell Biology Laboratory, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan.
Junko
J
Komeda
Cell Biology Laboratory, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan.
Jun
J
Itoh
Cell Biology Laboratory, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan.
Miki
M
Umemura
Cell Biology Laboratory, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan.
Ami
A
Kyusai
Laboratory of Immunology, Faculty of Pharmacy, Osaka Otani University, Tondabayashi, Osaka 584-8540, Japan.
Michio
0000-0002-7057-4996
M
Tomura
Department of Immunology, Graduate School of Medicine, Chiba University, Inage, Chiba 263-8522, Japan.
Toshinori
0000-0002-1434-2007
T
Nakayama
Keystone Symposia on Molecular and Cellular Biology, Silverthorne, CO 80498.
David L
DL
Woodland
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.
Jacob E
JE
Kohlmeier
Department of Immunology, Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan.|Anti-Aging Center, Kindai University, Osaka-Sayama, Osaka 589-8511, Japan.
Masaaki
M
Miyazawa
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D000099192:CD69 Antigens