PMID- 30850393
OWN - NLM
STAT- MEDLINE
DCOM- 20200408
LR  - 20220216
IS  - 2470-9468 (Electronic)
IS  - 2470-9468 (Linking)
VI  - 4
IP  - 33
DP  - 2019 Mar 8
TI  - Generation and persistence of human tissue-resident memory T cells in lung 
      transplantation.
LID - 10.1126/sciimmunol.aav5581 [doi]
LID - eaav5581
AB  - Tissue-resident memory T cells (T(RM)) maintain immunity in diverse sites as 
      determined in mouse models, whereas their establishment and role in human tissues 
      have been difficult to assess. Here, we investigated human lung T(RM) generation, 
      maintenance, and function in airway samples obtained longitudinally from human 
      leukocyte antigen (HLA)-disparate lung transplant recipients, where donor and 
      recipient T cells could be localized and tracked over time. Donor T cells persist 
      specifically in the lungs (and not blood) of transplant recipients and express 
      high levels of T(RM) signature markers including CD69, CD103, and CD49a, whereas 
      lung-infiltrating recipient T cells gradually acquire T(RM) phenotypes over 
      months in vivo. Single-cell transcriptome profiling of airway T cells reveals 
      that donor T cells comprise two T(RM)-like subsets with varying levels of 
      expression of T(RM)-associated genes, whereas recipient T cells comprised 
      non-T(RM) and similar T(RM)-like subpopulations, suggesting de novo T(RM) 
      generation. Transplant recipients exhibiting higher frequencies of persisting 
      donor T(RM) experienced fewer adverse clinical events such as primary graft 
      dysfunction and acute cellular rejection compared with recipients with low donor 
      T(RM) persistence, suggesting that monitoring T(RM) dynamics could be clinically 
      informative. Together, our results provide spatial and temporal insights into how 
      human T(RM) develop, function, persist, and affect tissue integrity within the 
      complexities of lung transplantation.
CI  - Copyright (c) 2019 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works.
FAU - Snyder, Mark E
AU  - Snyder ME
AUID- ORCID: 0000-0002-0092-9296
AD  - Department of Medicine, Columbia University Medical Center, New York, NY 10032, 
      USA.
AD  - Columbia Center for Translational Immunology, Columbia University Medical Center, 
      New York, NY 10032, USA.
FAU - Finlayson, Michael O
AU  - Finlayson MO
AUID- ORCID: 0000-0002-6886-3617
AD  - Department of Systems Biology, Columbia University Medical Center, New York, NY 
      10032, USA.
FAU - Connors, Thomas J
AU  - Connors TJ
AD  - Columbia Center for Translational Immunology, Columbia University Medical Center, 
      New York, NY 10032, USA.
AD  - Department of Pediatrics, Columbia University Medical Center, New York, NY 10032, 
      USA.
FAU - Dogra, Pranay
AU  - Dogra P
AUID- ORCID: 0000-0003-2031-9855
AD  - Columbia Center for Translational Immunology, Columbia University Medical Center, 
      New York, NY 10032, USA.
AD  - Department of Microbiology and Immunology, Columbia University Medical Center, 
      New York, NY 10032, USA.
FAU - Senda, Takashi
AU  - Senda T
AD  - Columbia Center for Translational Immunology, Columbia University Medical Center, 
      New York, NY 10032, USA.
AD  - Department of Surgery, Columbia University Medical Center, New York, NY 10032, 
      USA.
FAU - Bush, Erin
AU  - Bush E
AUID- ORCID: 0000-0001-7038-2321
AD  - Department of Systems Biology, Columbia University Medical Center, New York, NY 
      10032, USA.
FAU - Carpenter, Dustin
AU  - Carpenter D
AD  - Columbia Center for Translational Immunology, Columbia University Medical Center, 
      New York, NY 10032, USA.
AD  - Department of Surgery, Columbia University Medical Center, New York, NY 10032, 
      USA.
FAU - Marboe, Charles
AU  - Marboe C
AUID- ORCID: 0000-0001-6844-209X
AD  - Department of Pathology, Columbia University Medical Center, New York, NY 10032, 
      USA.
FAU - Benvenuto, Luke
AU  - Benvenuto L
AUID- ORCID: 0000-0001-8005-8074
AD  - Department of Medicine, Columbia University Medical Center, New York, NY 10032, 
      USA.
FAU - Shah, Lori
AU  - Shah L
AD  - Department of Medicine, Columbia University Medical Center, New York, NY 10032, 
      USA.
FAU - Robbins, Hilary
AU  - Robbins H
AD  - Department of Medicine, Columbia University Medical Center, New York, NY 10032, 
      USA.
FAU - Hook, Jaime L
AU  - Hook JL
AUID- ORCID: 0000-0002-6630-0060
AD  - Department of Medicine, Columbia University Medical Center, New York, NY 10032, 
      USA.
FAU - Sykes, Megan
AU  - Sykes M
AD  - Department of Medicine, Columbia University Medical Center, New York, NY 10032, 
      USA.
AD  - Columbia Center for Translational Immunology, Columbia University Medical Center, 
      New York, NY 10032, USA.
AD  - Department of Microbiology and Immunology, Columbia University Medical Center, 
      New York, NY 10032, USA.
FAU - D'Ovidio, Frank
AU  - D'Ovidio F
AD  - Department of Surgery, Columbia University Medical Center, New York, NY 10032, 
      USA.
FAU - Bacchetta, Matthew
AU  - Bacchetta M
AD  - Department of Surgery, Columbia University Medical Center, New York, NY 10032, 
      USA.
FAU - Sonett, Joshua R
AU  - Sonett JR
AD  - Department of Surgery, Columbia University Medical Center, New York, NY 10032, 
      USA.
FAU - Lederer, David J
AU  - Lederer DJ
AUID- ORCID: 0000-0001-5258-0228
AD  - Department of Medicine, Columbia University Medical Center, New York, NY 10032, 
      USA.
AD  - Department of Epidemiology, Mailman School of Public Health, Columbia University, 
      New York, NY 10032, USA.
FAU - Arcasoy, Selim
AU  - Arcasoy S
AD  - Department of Medicine, Columbia University Medical Center, New York, NY 10032, 
      USA.
AD  - Department of Pediatrics, Columbia University Medical Center, New York, NY 10032, 
      USA.
FAU - Sims, Peter A
AU  - Sims PA
AUID- ORCID: 0000-0002-3921-4837
AD  - Department of Systems Biology, Columbia University Medical Center, New York, NY 
      10032, USA.
FAU - Farber, Donna L
AU  - Farber DL
AUID- ORCID: 0000-0001-8236-9183
AD  - Columbia Center for Translational Immunology, Columbia University Medical Center, 
      New York, NY 10032, USA. df2396@cumc.columbia.edu.
AD  - Department of Microbiology and Immunology, Columbia University Medical Center, 
      New York, NY 10032, USA.
AD  - Department of Surgery, Columbia University Medical Center, New York, NY 10032, 
      USA.
LA  - eng
GR  - T32 HL105323/HL/NHLBI NIH HHS/United States
GR  - P01 AI106697/AI/NIAID NIH HHS/United States
GR  - R01 HL114626/HL/NHLBI NIH HHS/United States
GR  - R33 CA202827/CA/NCI NIH HHS/United States
GR  - R01 HL116136/HL/NHLBI NIH HHS/United States
GR  - K24 HL131937/HL/NHLBI NIH HHS/United States
GR  - U19 AI128949/AI/NIAID NIH HHS/United States
GR  - S10 RR027050/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Sci Immunol
JT  - Science immunology
JID - 101688624
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - Graft Rejection
MH  - Humans
MH  - *Immunologic Memory
MH  - Lung/*immunology
MH  - *Lung Transplantation
MH  - Male
MH  - Middle Aged
MH  - T-Lymphocytes/*immunology
MH  - Transcriptome
PMC - PMC6435356
MID - NIHMS1018690
COIS- Competing interests: The authors declare that they have no competing interests 
      with regard to this work.
EDAT- 2019/03/10 06:00
MHDA- 2020/04/09 06:00
PMCR- 2019/09/08
CRDT- 2019/03/10 06:00
PHST- 2018/09/27 00:00 [received]
PHST- 2019/01/28 00:00 [accepted]
PHST- 2019/03/10 06:00 [entrez]
PHST- 2019/03/10 06:00 [pubmed]
PHST- 2020/04/09 06:00 [medline]
PHST- 2019/09/08 00:00 [pmc-release]
AID - 4/33/eaav5581 [pii]
AID - 10.1126/sciimmunol.aav5581 [doi]
PST - ppublish
SO  - Sci Immunol. 2019 Mar 8;4(33):eaav5581. doi: 10.1126/sciimmunol.aav5581.