Unraveling the Multifaceted Nature of CD8 T Cell Exhaustion Provides the Molecular Basis for Therapeutic T Cell Reconstitution in Chronic Hepatitis B and C.
HBV
HCV
T cell exhaustion
chronic hepatitis
immune-modulation
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
28 09 2021
28 09 2021
Historique:
received:
13
08
2021
revised:
22
09
2021
accepted:
23
09
2021
entrez:
23
10
2021
pubmed:
24
10
2021
medline:
6
1
2022
Statut:
epublish
Résumé
In chronic hepatitis B and C virus infections persistently elevated antigen levels drive CD8+ T cells toward a peculiar differentiation state known as T cell exhaustion, which poses crucial constraints to antiviral immunity. Available evidence indicates that T cell exhaustion is associated with a series of metabolic and signaling deregulations and with a very peculiar epigenetic status which all together lead to reduced effector functions. A clear mechanistic network explaining how intracellular metabolic derangements, transcriptional and signaling alterations so far described are interconnected in a comprehensive and unified view of the T cell exhaustion differentiation profile is still lacking. Addressing this issue is of key importance for the development of innovative strategies to boost host immunity in order to achieve viral clearance. This review will discuss the current knowledge in HBV and HCV infections, addressing how innate immunity, metabolic derangements, extensive stress responses and altered epigenetic programs may be targeted to restore functionality and responsiveness of virus-specific CD8 T cells in the context of chronic virus infections.
Identifiants
pubmed: 34685543
pii: cells10102563
doi: 10.3390/cells10102563
pmc: PMC8533840
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministero della Salute
ID : RF 2013-02359333
Organisme : Regione Emilia-Romagna
ID : PRUa1RI-2012-006
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : 2017MPCWPY_002
Références
Front Immunol. 2020 May 12;11:849
pubmed: 32477347
Science. 2009 May 22;324(5930):1076-80
pubmed: 19461003
Nat Med. 2015 Jun;21(6):591-600
pubmed: 25962123
Cell. 2012 Sep 28;151(1):68-79
pubmed: 23021216
Cell. 2007 Feb 23;128(4):693-705
pubmed: 17320507
J Virol. 2018 Jan 2;92(2):
pubmed: 29093082
J Med Virol. 2017 Sep;89(9):1620-1628
pubmed: 28303593
Cell Rep. 2020 Jan 21;30(3):687-698.e6
pubmed: 31968246
Nature. 2006 Feb 9;439(7077):682-7
pubmed: 16382236
Nat Immunol. 2021 Feb;22(2):229-239
pubmed: 33398179
Nat Rev Immunol. 2020 Jan;20(1):55-70
pubmed: 31406325
Immunity. 2012 Dec 14;37(6):1130-44
pubmed: 23159438
J Hepatol. 2015 Jun;62(6):1237-45
pubmed: 25559326
Nat Immunol. 2009 Jan;10(1):29-37
pubmed: 19043418
Immunity. 2009 Aug 21;31(2):309-20
pubmed: 19664943
Nat Rev Mol Cell Biol. 2015 Jul;16(7):393-405
pubmed: 26122615
Int J Mol Sci. 2019 Jun 05;20(11):
pubmed: 31195619
Nat Commun. 2017 May 03;8:15050
pubmed: 28466857
Nat Rev Cancer. 2010 Apr;10(4):301-9
pubmed: 20332779
Cell. 2017 Jun 29;170(1):142-157.e19
pubmed: 28648661
Cell. 2010 Jun 11;141(6):970-81
pubmed: 20550933
Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15016-21
pubmed: 18809920
Biochim Biophys Acta. 2016 Dec;1864(12):1787-1800
pubmed: 27374990
Science. 2004 Mar 26;303(5666):2011-5
pubmed: 14976264
PLoS One. 2012;7(2):e32016
pubmed: 22359657
Annu Rev Immunol. 2019 Apr 26;37:457-495
pubmed: 30676822
Curr Opin Virol. 2018 Jun;30:9-17
pubmed: 29444493
Mol Cell. 2012 Nov 30;48(4):491-507
pubmed: 23200123
Nat Commun. 2015 Mar 26;6:6692
pubmed: 25809635
Lancet. 2017 Jun 24;389(10088):2492-2502
pubmed: 28434648
Nat Immunol. 2019 Mar;20(3):326-336
pubmed: 30778252
Science. 2016 Oct 28;354(6311):481-484
pubmed: 27708054
Mol Cell. 2005 Mar 18;17(6):855-68
pubmed: 15780941
PLoS Pathog. 2013 Mar;9(3):e1003208
pubmed: 23516358
J Hepatol. 2019 Nov;71(5):889-899
pubmed: 31295532
Hepatology. 2011 May;53(5):1494-503
pubmed: 21360567
Nature. 2019 Oct;574(7777):200-205
pubmed: 31582858
Nat Immunol. 2021 Aug;22(8):1020-1029
pubmed: 34312547
J Pharmacol Exp Ther. 2014 Jan;348(1):96-105
pubmed: 24133297
Sci Immunol. 2019 Feb 8;4(32):
pubmed: 30737354
PLoS One. 2018 Feb 14;13(2):e0190058
pubmed: 29444087
J Hepatol. 2021 Apr;74(4):783-793
pubmed: 33188902
FEBS J. 2015 May;282(9):1745-67
pubmed: 25223884
Immunity. 2016 Aug 16;45(2):358-73
pubmed: 27496729
J Hepatol. 2019 Nov;71(5):900-907
pubmed: 31306680
Science. 1998 Sep 11;281(5383):1677-9
pubmed: 9733515
Cancer Cell. 2019 Feb 11;35(2):238-255.e6
pubmed: 30753825
Nat Commun. 2021 May 14;12(1):2814
pubmed: 33990561
Nature. 2011 Jan 20;469(7330):343-9
pubmed: 21248841
Gut. 2019 May;68(5):905-915
pubmed: 30622109
Cell Rep. 2016 Aug 2;16(5):1243-1252
pubmed: 27452473
Nat Immunol. 2007 Jul;8(7):723-31
pubmed: 17546034
Immunity. 2019 Jan 15;50(1):195-211.e10
pubmed: 30635237
Hepatology. 2021 Oct;74(4):1737-1749
pubmed: 33704806
Cell Rep. 2020 Jan 7;30(1):112-123.e4
pubmed: 31914379
Trends Immunol. 2016 Dec;37(12):866-876
pubmed: 27720177
Nat Immunol. 2013 May;14(5):489-99
pubmed: 23563690
Nat Rev Genet. 2013 Jan;14(1):62-75
pubmed: 23247436
Hepatol Commun. 2019 Jul 08;3(10):1296-1310
pubmed: 31592075
Hepatology. 2010 Dec;52(6):1934-47
pubmed: 21064032
Liver Int. 2010 Aug;30(7):1019-26
pubmed: 20492507
Immunity. 2015 Feb 17;42(2):265-278
pubmed: 25680272
J Hepatol. 2020 Mar;72(3):420-430
pubmed: 31610223
Immunity. 2017 Apr 18;46(4):596-608
pubmed: 28410989
J Immunol. 2008 Apr 1;180(7):4476-86
pubmed: 18354169
J Med Chem. 2020 Sep 24;63(18):10188-10203
pubmed: 32407112
Lancet. 2019 Oct 19;394(10207):1451-1466
pubmed: 31631857
Immunity. 2016 May 17;44(5):1190-203
pubmed: 27192578
iScience. 2021 Jan 04;24(1):101969
pubmed: 33458618
Nature. 2009 Oct 22;461(7267):1071-8
pubmed: 19847258
J Exp Med. 2014 Mar 10;211(3):515-27
pubmed: 24590765
Nat Med. 2015 Apr;21(4):327-34
pubmed: 25799228
Nat Commun. 2013;4:2084
pubmed: 23811932
J Virol. 2007 Apr;81(8):4215-25
pubmed: 17287266
Gut. 2020 Oct 23;:
pubmed: 33097558
DNA Repair (Amst). 2018 Nov;71:177-182
pubmed: 30177435
Immunity. 2016 Aug 16;45(2):415-27
pubmed: 27533016
Cell. 2012 Sep 14;150(6):1182-95
pubmed: 22980979
Mol Cell. 2005 Dec 22;20(6):845-54
pubmed: 16359901
Trends Cell Biol. 2014 Aug;24(8):464-71
pubmed: 24786309
Blood. 2014 Jul 31;124(5):737-49
pubmed: 24951427
Front Immunol. 2019 May 31;10:1187
pubmed: 31214171
Hepatol Int. 2019 May;13(3):248-252
pubmed: 30607787
Immunity. 2021 Aug 10;54(8):1825-1840.e7
pubmed: 34270940
Med Microbiol Immunol. 2015 Feb;204(1):103-14
pubmed: 25535101
J Hepatol. 2019 Jun;70(6):1103-1113
pubmed: 30826436
Cell Rep. 2021 May 11;35(6):109120
pubmed: 33979613
Nat Med. 2013 Jul;19(7):859-68
pubmed: 23836236
Trends Immunol. 2015 Feb;36(2):81-91
pubmed: 25592731
Front Immunol. 2020 May 28;11:1037
pubmed: 32547550
Cytokine Growth Factor Rev. 2017 Jun;35:63-70
pubmed: 28363691
J Exp Med. 2012 Dec 17;209(13):2441-53
pubmed: 23183047
PLoS One. 2012;7(10):e47648
pubmed: 23112829
Nat Commun. 2020 Jan 30;11(1):604
pubmed: 32001678
Immunity. 2010 Jan 29;32(1):79-90
pubmed: 20096607
Semin Immunol. 2016 Oct;28(5):505-513
pubmed: 27712958
Nature. 2017 May 25;545(7655):452-456
pubmed: 28514453
Cell. 2017 May 4;169(4):570-586
pubmed: 28475890
J Virol. 2003 Apr;77(8):4911-27
pubmed: 12663797
Gastroenterology. 2010 Feb;138(2):682-93, 693.e1-4
pubmed: 19800335
Nat Immunol. 2021 Aug;22(8):1030-1041
pubmed: 34312544
J Cell Sci. 2012 Sep 1;125(Pt 17):3939-48
pubmed: 23104738
Science. 2013 Oct 11;342(6155):1242454
pubmed: 24115444
Gastroenterology. 2012 Dec;143(6):1576-1585.e4
pubmed: 22929808
Nat Rev Immunol. 2015 Aug;15(8):486-99
pubmed: 26205583
Nature. 2019 Jul;571(7764):211-218
pubmed: 31207603
J Hepatol. 2014 Dec;61(6):1212-9
pubmed: 25016223
Cell Rep. 2020 Aug 25;32(8):108078
pubmed: 32846135
Annu Rev Immunol. 2018 Apr 26;36:461-488
pubmed: 29677474
Nat Immunol. 2017 May;18(5):573-582
pubmed: 28288100
Nat Immunol. 2014 Oct;15(10):965-72
pubmed: 25151490
Immunity. 2020 May 19;52(5):825-841.e8
pubmed: 32396847
Nat Rev Immunol. 2016 Dec;16(12):741-750
pubmed: 27667712
Immunity. 2013 Nov 14;39(5):819-32
pubmed: 24238339
Nature. 2017 May 4;545(7652):60-65
pubmed: 28397821
Immunity. 2017 Oct 17;47(4):648-663.e8
pubmed: 29045899
Radiat Res. 1985 Jan;101(1):4-15
pubmed: 3155867
Nature. 2016 Sep 15;537(7620):417-421
pubmed: 27501248
Nat Rev Gastroenterol Hepatol. 2019 Nov;16(11):662-675
pubmed: 31548710
J Immunol. 1999 Apr 15;162(8):4472-81
pubmed: 10201984
Front Immunol. 2021 Feb 03;11:592328
pubmed: 33613516
J Virol. 1994 Jul;68(7):4700-4
pubmed: 7911534
BMC Immunol. 2020 Apr 21;21(1):22
pubmed: 32316916
PLoS Pathog. 2014 Jan;10(1):e1003856
pubmed: 24391505
PLoS Pathog. 2016 Jan 07;12(1):e1005349
pubmed: 26741490
Nat Immunol. 2017 Apr;18(4):422-432
pubmed: 28218746
Front Immunol. 2017 Apr 11;8:429
pubmed: 28443098
Sci Rep. 2020 Jul 29;10(1):12767
pubmed: 32728070
Science. 2012 Nov 30;338(6111):1220-5
pubmed: 23197535
Immunity. 2010 Jan 29;32(1):91-103
pubmed: 20096608
Science. 2016 Dec 2;354(6316):1165-1169
pubmed: 27789799
Annu Rev Virol. 2015 Nov;2(1):573-97
pubmed: 26958929
Annu Rev Immunol. 2013;31:259-83
pubmed: 23298210
J Exp Med. 2015 Aug 24;212(9):1345-60
pubmed: 26261266
Gastroenterology. 2018 May;154(6):1764-1777.e7
pubmed: 29378197
Nat Immunol. 2014 Sep;15(9):884-93
pubmed: 25029552
Gut. 2019 May;68(5):893-904
pubmed: 30580250
Life Sci. 2021 Oct 1;282:119803
pubmed: 34237310
J Clin Invest. 2018 Aug 31;128(9):3813-3818
pubmed: 29905573
Gastroenterology. 2013 Jun;144(7):1508-17, 1517.e1-10
pubmed: 23415804
Immunity. 2014 Nov 20;41(5):802-14
pubmed: 25464856
Viruses. 2021 Apr 09;13(4):
pubmed: 33918831
Science. 2016 Dec 2;354(6316):1160-1165
pubmed: 27789795
Lancet Gastroenterol Hepatol. 2018 Mar;3(3):192-202
pubmed: 29870733
Nat Rev Immunol. 2015 Sep 15;15(9):574-84
pubmed: 26272293
Nat Rev Mol Cell Biol. 2021 Feb;22(2):119-141
pubmed: 33353981
PLoS One. 2017 Jan 5;12(1):e0169631
pubmed: 28056062
Nat Rev Immunol. 2018 Oct;18(10):648-659
pubmed: 30089912
Front Immunol. 2016 May 03;7:172
pubmed: 27199994
Immunity. 2011 Dec 23;35(6):871-82
pubmed: 22195744
Curr Opin Virol. 2016 Jun;18:109-16
pubmed: 27318098
Hepatol Commun. 2019 Oct 01;3(10):1289-1292
pubmed: 31592063
Hepatology. 2021 Jul;74(1):55-71
pubmed: 33368377
Curr Top Microbiol Immunol. 2014;380:129-44
pubmed: 25004816
Nat Med. 2017 Mar;23(3):327-336
pubmed: 28165481
Nat Rev Immunol. 2014 Jul;14(7):435-46
pubmed: 24962260
Hepatology. 2021 Jan;73(1):53-67
pubmed: 32246499