HCV-specific CD4+ T cells of patients with acute and chronic HCV infection display high expression of TIGIT and other co-inhibitory molecules.
Acute Disease
Adult
Aged
CD4-Positive T-Lymphocytes
/ immunology
Female
Hepacivirus
/ immunology
Hepatitis A Virus Cellular Receptor 2
/ blood
Hepatitis C
/ immunology
Hepatitis C, Chronic
/ immunology
Histocompatibility Antigens Class II
/ metabolism
Humans
Male
Middle Aged
Programmed Cell Death 1 Receptor
/ blood
Receptors, Immunologic
/ blood
Receptors, OX40
/ blood
Young Adult
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
23 07 2019
23 07 2019
Historique:
received:
11
02
2019
accepted:
03
07
2019
entrez:
25
7
2019
pubmed:
25
7
2019
medline:
4
11
2020
Statut:
epublish
Résumé
The combined regulation of a network of inhibitory and activating T cell receptors may be a critical step in the development of chronic HCV infection. Ex vivo HCV MHC class I + II tetramer staining and bead-enrichment was performed with baseline and longitudinal PBMC samples of a cohort of patients with acute, chronic and spontaneously resolved HCV infection to assess the expression pattern of the co-inhibitory molecule TIGIT together with PD-1, BTLA, Tim-3, as well as OX40 and CD226 (DNAM-1) of HCV-specific CD4+ T cells, and in a subset of patients of HCV-specific CD8+ T cells. As the main result, we found a higher expression level of TIGIT+ PD-1+ on HCV-specific CD4+ T cells during acute and chronic HCV infection compared to patients with spontaneously resolved HCV infection (p < 0,0001). Conversely, expression of the complementary co-stimulatory receptor of TIGIT, CD226 (DNAM-1) was significantly decreased on HCV-specific CD4+ T cells during chronic infection. The predominant phenotype of HCV-specific CD4+ T cells during acute and chronic infection was TIGIT+, PD-1+, BTLA+, Tim-3-. This comprehensive phenotypic study confirms TIGIT together with PD-1 as a discriminatory marker of dysfunctional HCV-specific CD4+ T cells.
Identifiants
pubmed: 31337800
doi: 10.1038/s41598-019-47024-8
pii: 10.1038/s41598-019-47024-8
pmc: PMC6650447
doi:
Substances chimiques
BTLA protein, human
0
HAVCR2 protein, human
0
Hepatitis A Virus Cellular Receptor 2
0
Histocompatibility Antigens Class II
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Receptors, Immunologic
0
Receptors, OX40
0
TIGIT protein, human
0
TNFRSF4 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10624Références
Sci Rep. 2018 Mar 19;8(1):4789
pubmed: 29555909
Eur J Immunol. 2010 Apr;40(4):949-54
pubmed: 20201043
J Clin Invest. 2003 Sep;112(6):831-42
pubmed: 12975468
J Infect Dis. 2010 May 1;201(9):1371-80
pubmed: 20331378
J Clin Invest. 2006 Jun;116(6):1675-85
pubmed: 16710479
J Clin Invest. 2015 May;125(5):2046-58
pubmed: 25866972
Science. 2003 Oct 24;302(5645):659-62
pubmed: 14576438
J Virol. 2002 Dec;76(24):12584-95
pubmed: 12438584
Science. 2016 Dec 2;354(6316):1165-1169
pubmed: 27789799
Cancer Cell. 2014 Dec 8;26(6):923-937
pubmed: 25465800
J Virol. 2017 Nov 14;91(23):
pubmed: 28904197
Nat Immunol. 2011 Jun;12(6):492-9
pubmed: 21739672
Sci Rep. 2017 Jan 13;7:40354
pubmed: 28084312
Cytometry A. 2011 Feb;79(2):167-74
pubmed: 21265010
Proc Natl Acad Sci U S A. 2017 Feb 7;114(6):E908-E909
pubmed: 28137888
N Engl J Med. 2001 Jul 5;345(1):41-52
pubmed: 11439948
PLoS Pathog. 2011 May;7(5):e1002045
pubmed: 21625589
PLoS Pathog. 2009 Feb;5(2):e1000313
pubmed: 19247441
Blood. 2018 Oct 18;132(16):1689-1694
pubmed: 29986909
Hum Immunol. 2017 Feb;78(2):88-94
pubmed: 27780790
Oncoimmunology. 2017 Sep 21;7(1):e1371399
pubmed: 29296521
J Virol. 2006 Nov;80(22):11398-403
pubmed: 16956940
J Virol. 2009 Sep;83(18):9122-30
pubmed: 19587053
Gastroenterology. 2014 Feb;146(2):550-61
pubmed: 24148617
Nat Immunol. 2009 Jan;10(1):48-57
pubmed: 19011627
Int Immunol. 2010 Jan;22(1):13-23
pubmed: 19880580
JCI Insight. 2018 Jul 26;3(14):
pubmed: 30046006
Annu Rev Microbiol. 2004;58:391-424
pubmed: 15487943
J Hepatol. 2017 Feb;66(2):282-287
pubmed: 27650285
Oncoimmunology. 2018 May 24;7(8):e1466769
pubmed: 30221069
Ann Intern Med. 2013 Feb 19;158(4):235-45
pubmed: 23420232
J Immunol. 2008 Dec 15;181(12):8215-25
pubmed: 19050238
Cancer Immunol Immunother. 2018 Nov;67(11):1659-1667
pubmed: 30232519
Hepatology. 2001 Jan;33(1):267-76
pubmed: 11124845
J Hepatol. 2015 Jan;62(1):31-40
pubmed: 25131771
PLoS One. 2014 Aug 21;9(8):e105703
pubmed: 25144233
Cancer Cell. 2014 Dec 8;26(6):785-787
pubmed: 25490444
PLoS Pathog. 2016 Jul 14;12(7):e1005761
pubmed: 27415008
Antiviral Res. 2015 Feb;114:96-105
pubmed: 25433310
Nat Immunol. 2003 Sep;4(9):835-42
pubmed: 12942084
Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14733-8
pubmed: 20679213
J Exp Med. 2012 Jan 16;209(1):61-75
pubmed: 22213804
Cell Immunol. 2017 Mar;313:1-9
pubmed: 28104239
Gastroenterology. 2019 Jan;156(2):418-430
pubmed: 30268785
Nat Rev Immunol. 2015 Aug;15(8):486-99
pubmed: 26205583
J Virol. 2008 Mar;82(6):3154-60
pubmed: 18160439
PLoS Pathog. 2012 Sep;8(9):e1002913
pubmed: 22969431
Nat Immunol. 2008 Feb;9(2):122-4
pubmed: 18204424
J Exp Med. 2001 Nov 19;194(10):1395-406
pubmed: 11714747
Lancet. 1995 Oct 14;346(8981):1006-7
pubmed: 7475549
PLoS Pathog. 2016 Jan 07;12(1):e1005349
pubmed: 26741490
J Immunol. 2013 Nov 15;191(10):5026-35
pubmed: 24101548
PLoS Pathog. 2010 Jun 10;6(6):e1000947
pubmed: 20548953
Virology. 2012 Aug 1;429(2):163-70
pubmed: 22579352
Lancet Infect Dis. 2012 May;12(5):408-14
pubmed: 22541630
J Virol. 2007 Sep;81(17):9249-58
pubmed: 17567698
Immunity. 2014 Feb 20;40(2):289-302
pubmed: 24530057