Could a loss of memory T cells limit responses to hepatitis C virus (HCV) antigens in blood leucocytes from patients chronically infected with HCV before and during pegylated interferon-alpha and ribavirin therapy?
The proportions and activation status of T cells may influence responses to hepatitis C virus (HCV) and treatment outcome in patients receiving pegylated interferon (IFN)-alpha/ribavirin therapy. We confirmed that IFN-gamma enzyme-linked immunospot (ELISPOT) responses to HCV are poor in HCV patients and showed that responses to HCV and cytomegalovirus (CMV) antigens decrease during therapy. This was most apparent in patients with sustained virological response (SVR). Baseline frequencies of CD4+ effector memory (TEM) T cells were lower in SVR than non-SVR. Proportions of CD4+ and CD8+ TEM and terminally differentiated effector memory (TEMRA) T cells declined on therapy in SVR, as did proportions of Fas+ CD8+ TEMRA T cells. Baseline frequencies of programmed death (PD)-1-expressing CD4+ TEM and TEMRA T-cells were higher in SVR. Therapy increased percentages of PD-1+ CD4+ central memory (TCM) T cells and PD-1+ CD8+ TEM and TEMRA T cells in SVR. We conclude that successful therapy depletes circulating antigen-specific CD4+ T cell responses. This paralleled decreases in proportions of effector memory T cells and higher percentages of CD4+ TCM T cells expressing PD-1.
Lee
S
S
Department of Microbiology and Infectious Disease, Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital, School of Pathology and Laboratory Medicine, University of Western Australia, WA, Australia. silvialee@meddent.uwa.edu.au
Hammond
T
T
Watson
M W
MW
Flexman
J P
JP
Cheng
W
W
Fernandez
S
S
Price
P
P
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000956:Antigens, Viral / Q000276:immunology; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D061026:Programmed Cell Death 1 Receptor; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D055815:Young Adult
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D000998:Antiviral Agents; D051017:Apoptosis Regulatory Proteins; D018936:Hepatitis C Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D007371:Interferon-gamma; C100416:peginterferon alfa-2a
Viral Immunol. 2009 Feb;22(1):39-48
19210227
J Hepatol. 2008 Sep;49(3):329-38
18644644
Hepatology. 1996 Aug;24(2):289-93
8690394
J Exp Med. 1992 Jul 1;176(1):245-53
1377224
J Immunol. 2005 Dec 15;175(12):8415-23
16339584
Gastroenterology. 2002 Oct;123(4):1070-83
12360469
Hepatology. 2001 Jan;33(1):267-76
11124845
Science. 2003 Oct 24;302(5645):659-62
14576438
Blood. 2009 Jan 22;113(4):769-74
18583570
Antivir Ther. 2007;12(4):459-68
17668554
Hepatology. 2002 Sep;36(3):743-54
12198669
J Exp Med. 2000 May 1;191(9):1499-512
10790425
J Infect Dis. 2003 Nov 15;188(10):1533-6
14624379
J Exp Med. 2003 Jun 16;197(12):1645-55
12810686
Nature. 2005 Aug 18;436(7053):967-72
16107837
Clin Exp Immunol. 2006 Nov;146(2):270-7
17034579
Annu Rev Immunol. 2008;26:677-704
18173375
J Allergy Clin Immunol. 2005 Nov;116(5):949-59; quiz 960
16275360
Viral Immunol. 2001;14(2):169-79
11398812
J Infect Dis. 2009 Mar 15;199(6):819-28
19434929
J Hepatol. 2006 Mar;44(3):475-83
16426698
Annu Rev Immunol. 2002;20:551-79
11861612
J Clin Virol. 2004 Nov;31(3):227-34
15465417
J Immunol Methods. 2007 Jan 30;319(1-2):41-52
17173927
Viral Immunol. 2005;18(1):197-204
15802964
Clin Immunol Immunopathol. 1994 Dec;73(3):350-7
7955564
Clin Chem. 2002 Dec;48(12):2147-54
12446470
Eur J Immunol. 1998 Nov;28(11):3448-55
9842887
Hepatology. 2004 Nov;40(5):1062-71
15486925
HIV Med. 2003 Apr;4(2):120-6
12702132
Gut. 2006 Oct;55(10):1484-7
16543291
J Viral Hepat. 2008 Jan;15(1):2-11
18088238
Eur J Immunol. 2005 Jun;35(6):1681-91
15902688
J Exp Med. 2001 Nov 19;194(10):1395-406
11714747
Blood. 2003 Apr 1;101(7):2711-20
12433688
Immunity. 2005 Mar;22(3):329-41
15780990
J Hepatol. 2007 Nov;47(5):632-41
17560677
Antivir Ther. 2007;12(3):303-16
17591020
J Virol. 2007 Sep;81(17):9249-58
17567698
Clin Immunol. 2007 Apr;123(1):40-9
17239662