Transcriptomic and clonal characterization of T cells in the human central nervous system.


Journal

Science immunology
ISSN: 2470-9468
Titre abrégé: Sci Immunol
Pays: United States
ID NLM: 101688624

Informations de publication

Date de publication:
18 09 2020
Historique:
received: 24 03 2020
accepted: 26 08 2020
entrez: 19 9 2020
pubmed: 20 9 2020
medline: 11 1 2022
Statut: ppublish

Résumé

T cells provide critical immune surveillance to the central nervous system (CNS), and the cerebrospinal fluid (CSF) is thought to be a main route for their entry. Further characterization of the state of T cells in the CSF in healthy individuals is important for understanding how T cells provide protective immune surveillance without damaging the delicate environment of the CNS and providing tissue-specific context for understanding immune dysfunction in neuroinflammatory disease. Here, we have profiled T cells in the CSF of healthy human donors and have identified signatures related to cytotoxic capacity and tissue adaptation that are further exemplified in clonally expanded CSF T cells. By comparing profiles of clonally expanded T cells obtained from the CSF of patients with multiple sclerosis (MS) and healthy donors, we report that clonally expanded T cells from the CSF of patients with MS have heightened expression of genes related to T cell activation and cytotoxicity.

Identifiants

pubmed: 32948672
pii: 5/51/eabb8786
doi: 10.1126/sciimmunol.abb8786
pmc: PMC8567322
mid: NIHMS1657097
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NCI NIH HHS
ID : R01 CA227473
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI039671
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA121974
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI089992
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI073748
Pays : United States
Organisme : NINDS NIH HHS
ID : R25 NS079193
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI045757
Pays : United States

Informations de copyright

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Références

Nature. 2018 Nov;563(7731):347-353
pubmed: 30429548
Immunity. 2019 Feb 19;50(2):493-504.e7
pubmed: 30737144
J Immunol. 2014 Oct 15;193(8):3959-65
pubmed: 25225667
Front Immunol. 2018 Jul 30;9:1770
pubmed: 30131803
Mod Rheumatol. 2020 Sep;30(5):930-936
pubmed: 31512538
Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2428-33
pubmed: 14983026
Neuron. 2017 May 17;94(4):759-773.e8
pubmed: 28521131
Front Immunol. 2015 Nov 26;6:604
pubmed: 26635816
Brain. 2018 Jul 1;141(7):2066-2082
pubmed: 29873694
Nature. 2018 Jun;558(7710):454-459
pubmed: 29899446
Acta Neuropathol. 2017 Sep;134(3):383-401
pubmed: 28624961
J Invest Dermatol. 2014 May;134(5):1428-1435
pubmed: 24226419
Neurol Neuroimmunol Neuroinflamm. 2019 Jul 01;6(5):e587
pubmed: 31355321
Proc Natl Acad Sci U S A. 2004 May 25;101(21):8180-5
pubmed: 15141078
Front Immunol. 2019 Mar 07;10:400
pubmed: 30899267
Trends Immunol. 2015 Sep;36(9):556-64
pubmed: 26282885
Cell Rep. 2017 Sep 19;20(12):2921-2934
pubmed: 28930685
Science. 2015 Jan 23;347(6220):400-6
pubmed: 25477212
Clin Exp Immunol. 2002 Sep;129(3):510-8
pubmed: 12197893
Neuron. 2018 Feb 21;97(4):742-768
pubmed: 29470968
Eur J Immunol. 2010 Aug;40(8):2174-81
pubmed: 20486123
Sci Immunol. 2019 Mar 8;4(33):
pubmed: 30850393
Neurology. 2018 Aug 28;91(9):e867-e877
pubmed: 30054439
Semin Immunopathol. 2015 May;37(3):261-70
pubmed: 25898888
Nat Commun. 2018 Nov 2;9(1):4593
pubmed: 30389931
Arch Neurol. 2010 Aug;67(8):923-30
pubmed: 20697042
Science. 2016 Apr 22;352(6284):459-63
pubmed: 27102484
Eur J Immunol. 2017 Jun;47(6):946-953
pubmed: 28475283
J Clin Invest. 2019 Nov 1;129(11):4758-4768
pubmed: 31566584
PLoS One. 2017 Sep 7;12(9):e0181538
pubmed: 28880903
Nat Immunol. 2013 Dec;14(12):1285-93
pubmed: 24162775
Front Immunol. 2019 Apr 17;10:783
pubmed: 31105690
Nat Commun. 2019 Oct 17;10(1):4706
pubmed: 31624246
Nat Biotechnol. 2019 Dec;37(12):1482-1492
pubmed: 31796933
Front Immunol. 2018 Oct 16;9:2394
pubmed: 30386342
Nat Immunol. 2013 May;14(5):489-99
pubmed: 23563690
Nat Neurosci. 2019 Dec;22(12):2098-2110
pubmed: 31740814
J Immunol. 2016 May 1;196(9):3920-6
pubmed: 27001957
Nature. 2016 Jul 21;535(7612):425-9
pubmed: 27409813
Cell. 2018 Jul 26;174(3):716-729.e27
pubmed: 29961576
Nat Commun. 2020 Jan 14;11(1):247
pubmed: 31937773
Immunity. 2018 Jul 17;49(1):80-92.e7
pubmed: 29958803
J Exp Med. 2019 Oct 7;216(10):2412-2426
pubmed: 31337737
PLoS One. 2008 Jul 02;3(7):e2559
pubmed: 18596942
Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):17872-9
pubmed: 20923878
PLoS One. 2013 Jun 18;8(6):e66188
pubmed: 23822975
Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8389-94
pubmed: 12829791
J Clin Invest. 2010 May;120(5):1368-79
pubmed: 20440079
Exp Cell Res. 2011 Mar 10;317(5):620-31
pubmed: 21376175
J Crohns Colitis. 2019 Jul 25;13(7):905-915
pubmed: 30715262
Mult Scler. 2016 Apr;22(4):483-93
pubmed: 26163073
J Clin Invest. 2017 Sep 1;127(9):3210-3219
pubmed: 28862640
Nature. 1990 Jul 12;346(6280):183-7
pubmed: 1694970
Brain. 2011 Feb;134(Pt 2):534-41
pubmed: 21216828
Immunity. 2017 Jun 20;46(6):891-909
pubmed: 28636958
Glia. 2020 Jun;68(6):1291-1303
pubmed: 31958186
Cell. 2015 Jul 2;162(1):184-97
pubmed: 26095251
Elife. 2018 Feb 28;7:
pubmed: 29488879
Curr Neurol Neurosci Rep. 2011 Oct;11(5):455-63
pubmed: 21725901
J Neurosci. 2004 May 19;24(20):4849-58
pubmed: 15152045
Ther Adv Neurol Disord. 2009 Mar;2(2):115-28
pubmed: 21180646
Cell Res. 2006 Jan;16(1):3-10
pubmed: 16467870
Nat Neurosci. 2017 Feb;20(2):136-144
pubmed: 28092660
Nat Neurosci. 2011 Nov 27;15(2):274-83
pubmed: 22119903
J Immunol. 2014 Mar 15;192(6):2551-63
pubmed: 24510966
J Neuroimmunol. 2012 Jul 15;248(1-2):53-7
pubmed: 22579051
Cell. 2019 Jul 25;178(3):714-730.e22
pubmed: 31348891
Nature. 2020 Jan;577(7790):399-404
pubmed: 31915375
Brain Behav Immun. 2017 Aug;64:71-79
pubmed: 28336414
Science. 2014 Nov 28;346(6213):1250689
pubmed: 25342659
Cell. 2019 Sep 5;178(6):1493-1508.e20
pubmed: 31474370
J Neuroimmunol. 2006 Nov;180(1-2):17-28
pubmed: 16945427
N Engl J Med. 1985 May 30;312(22):1405-11
pubmed: 2985995
Immunity. 2018 Feb 20;48(2):202-213
pubmed: 29466753
JCI Insight. 2018 Sep 20;3(18):
pubmed: 30232286
Genome Biol. 2015 Dec 10;16:278
pubmed: 26653891
Am J Transplant. 2008 Mar;8(3):627-36
pubmed: 18294159
Nat Immunol. 2019 Dec;20(12):1692-1699
pubmed: 31745340
J Exp Med. 2001 Oct 1;194(7):915-26
pubmed: 11581314
Arthritis Res Ther. 2006;8(6):R166
pubmed: 17078892
PLoS One. 2016 Jan 29;11(1):e0148351
pubmed: 26824609
Nature. 2019 Jul;571(7764):205-210
pubmed: 31270459
Immunity. 2020 May 19;52(5):808-824.e7
pubmed: 32433949
J Exp Med. 2019 Dec 2;216(12):2748-2762
pubmed: 31558615
J Immunol. 2018 Jan 1;200(1):336-346
pubmed: 29180490

Auteurs

Jenna L Pappalardo (JL)

Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT 06511, USA.

Le Zhang (L)

Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT 06511, USA.

Maggie K Pecsok (MK)

Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT 06511, USA.

Kelly Perlman (K)

Montreal Neurologic Institute, Montreal, Quebec, Canada.

Chrysoula Zografou (C)

Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT 06511, USA.

Khadir Raddassi (K)

Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT 06511, USA.

Ahmad Abulaban (A)

Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT 06511, USA.

Smita Krishnaswamy (S)

Departments of Genetics and Computer Science, Yale School of Medicine, New Haven, CT 06511, USA.

Jack Antel (J)

Montreal Neurologic Institute, Montreal, Quebec, Canada.

David van Dijk (D)

Departments of Internal Medicine (Cardiology), Cardiovascular Research Center, and Computer Science, New Haven, CT 06511, USA. david.vandijk@yale.edu david.hafler@yale.edu.

David A Hafler (DA)

Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT 06511, USA. david.vandijk@yale.edu david.hafler@yale.edu.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH