title: Programmed death-1 is a marker for abnormal distribution of naive/memory T cell subsets in HIV-1 infection.
abstract: Chronic activation of T cells is a hallmark of HIV-1 infection and plays an important role in disease progression. We previously showed that the engagement of the inhibitory receptor programmed death (PD)-1 on HIV-1-specific CD4(+) and CD8(+) T cells leads to their functional exhaustion in vitro. However, little is known about the impact of PD-1 expression on the turnover and maturation status of T cells during the course of the disease. In this study, we show that PD-1 is upregulated on all T cell subsets, including naive, central memory, and transitional memory T cells in HIV-1-infected subjects. PD-1 is expressed at similar levels on most CD4(+) T cells during the acute and the chronic phase of disease and identifies cells that have recently entered the cell cycle. In contrast, PD-1 expression is dramatically increased in CD8(+) T cells during the transition from acute to chronic infection, and this is associated with reduced levels of cell proliferation. The failure to downregulate expression of PD-1 in most T cells during chronic HIV-1 infection is associated with persistent alterations in the distribution of T cell subsets and is associated with impaired responses to IL-7. Our findings identify PD-1 as a marker for aberrant distribution of T cell subsets in HIV-1 infection.
authors.affiliation: Laboratoire d'Immunologie, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Saint-Luc, Montreal, Quebec H2X 1P1, Canada.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Breton
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chomont
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takata
authors.forename: Rémi
authors.initials: R
authors.lastname: Fromentin
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ahlers
authors.forename: Abdelali
authors.initials: A
authors.lastname: Filali-Mouhim
authors.forename: Catherine
authors.initials: C
authors.lastname: Riou
authors.forename: Mohamed-Rachid
authors.initials: MR
authors.lastname: Boulassel
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Bader
authors.initials: B
authors.lastname: Yassine-Diab
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sékaly
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
references.citation: Eur J Immunol. 2002 Mar;32(3):634-43
references.pmid: 11857337
references.citation: J Exp Med. 2007 Sep 3;204(9):2171-85
references.pmid: 17724130
references.citation: J Immunol. 2007 Aug 1;179(3):1979-87
references.pmid: 17641065
references.citation: Curr Opin Investig Drugs. 2010 Dec;11(12):1354-9
references.pmid: 21154117
references.citation: Blood. 2007 Jun 1;109(11):4671-8
references.pmid: 17272504
references.citation: Immunol Cell Biol. 2007 Jan;85(1):6-15
references.pmid: 17146463
references.citation: J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Oct 1;16(2):83-92
references.pmid: 9358102
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17765-70
references.pmid: 17968013
references.citation: AIDS. 2003 Sep 5;17(13):1881-8
references.pmid: 12960820
references.citation: PLoS Biol. 2004 Feb;2(2):E20
references.pmid: 14966528
references.citation: J Acquir Immune Defic Syndr. 2000 Nov 1;25(3):203-11
references.pmid: 11115950
references.citation: Nat Med. 2006 Dec;12(12):1365-71
references.pmid: 17115046
references.citation: Nature. 2006 Feb 9;439(7077):682-7
references.pmid: 16382236
references.citation: Curr Drug Targets Infect Disord. 2005 Jun;5(2):121-9
references.pmid: 15975018
references.citation: Nature. 1998 Dec 17;396(6712):690-5
references.pmid: 9872319
references.citation: J Immunol. 2001 Dec 1;167(11):6663-8
references.pmid: 11714838
references.citation: Cell Death Differ. 2005 Aug;12 Suppl 1:845-54
references.pmid: 15832178
references.citation: J Immunol. 2010 Nov 1;185(9):5417-24
references.pmid: 20935203
references.citation: Mol Med. 2011 Mar-Apr;17(3-4):229-40
references.pmid: 21103670
references.citation: Clin Exp Immunol. 2009 Jul;157(1):90-7
references.pmid: 19659774
references.citation: AIDS Rev. 2003 Jul-Sep;5(3):172-7
references.pmid: 14598566
references.citation: J Exp Med. 2007 Oct 1;204(10):2321-33
references.pmid: 17785507
references.citation: J Clin Invest. 2011 Mar;121(3):998-1008
references.pmid: 21393864
references.citation: J Immunol. 2008 Nov 15;181(10):6738-46
references.pmid: 18981091
references.citation: J Immunol. 2005 Nov 1;175(9):6117-22
references.pmid: 16237108
references.citation: J Immunol. 2002 Jun 1;168(11):5954-8
references.pmid: 12023402
references.citation: Immunol Cell Biol. 2004 Feb;82(1):38-46
references.pmid: 14984593
references.citation: J Immunol. 2007 Jan 15;178(2):788-97
references.pmid: 17202340
references.citation: Blood. 2000 Jan 1;95(1):249-55
references.pmid: 10607709
references.citation: J Exp Med. 2000 Oct 2;192(7):1027-34
references.pmid: 11015443
references.citation: J Immunol. 2002 Sep 15;169(6):3400-6
references.pmid: 12218162
references.citation: J Infect Dis. 1999 Apr;179(4):859-70
references.pmid: 10068581
references.citation: J Exp Med. 2006 Oct 2;203(10):2281-92
references.pmid: 16954372
references.citation: J Immunol. 2005 Dec 15;175(12):8415-23
references.pmid: 16339584
references.citation: J Immunol. 2010 Jan 1;184(1):476-87
references.pmid: 19949078
references.citation: Nature. 2006 Sep 21;443(7109):350-4
references.pmid: 16921384
references.citation: Annu Rev Immunol. 2005;23:515-48
references.pmid: 15771580
references.citation: Antivir Chem Chemother. 2001 May;12(3):133-50
references.pmid: 12959322
references.citation: Nat Med. 2006 Oct;12(10):1198-202
references.pmid: 16917489
references.citation: Nature. 2009 Mar 12;458(7235):206-10
references.pmid: 19078956
references.citation: J Clin Invest. 2002 Oct;110(8):1133-9
references.pmid: 12393849
references.citation: Nat Med. 2002 Apr;8(4):379-85
references.pmid: 11927944
references.citation: Annu Rev Immunol. 2003;21:265-304
references.pmid: 12524385
references.citation: J Virol. 2008 Feb;82(4):1870-83
references.pmid: 18077723
references.citation: AIDS. 2005 Dec 2;19(18):2077-86
references.pmid: 16284456
references.citation: J Acquir Immune Defic Syndr (1988). 1993 Aug;6(8):904-12
references.pmid: 7686224
references.citation: J Virol. 2009 Apr;83(8):3556-67
references.pmid: 19193811
references.citation: Virol J. 2011 Jun 07;8:279
references.pmid: 21645420
references.citation: J Acquir Immune Defic Syndr. 2011 Feb 1;56(2):118-24
references.pmid: 20980914
references.citation: Blood. 2003 Apr 1;101(7):2711-20
references.pmid: 12433688
references.citation: Immunity. 2004 Dec;21(6):757-68
references.pmid: 15589165
references.citation: Virol J. 2010 Nov 12;7:310
references.pmid: 21070674
references.citation: PLoS One. 2010 Aug 20;5(8):e12303
references.pmid: 20808830