title: HIV-1 impairs in vitro priming of naïve T cells and gives rise to contact-dependent suppressor T cells.
abstract: Priming of T cells in lymphoid tissues of HIV-infected individuals occurs in the presence of HIV-1. DC in this milieu activate T cells and disseminate HIV-1 to newly activated T cells, the outcome of which may have serious implications in the development of optimal antiviral responses. We investigated the effects of HIV-1 on DC-naïve T-cell interactions using an allogeneic in vitro system. Our data demonstrate a dramatic decrease in the primary expansion of naïve T cells when cultured with HIV-1-exposed DC. CD4(+) and CD8(+) T cells showed enhanced expression of PD-1 and TRAIL, whereas CTLA-4 expression was observed on CD4(+) T cells. It is worth noting that T cells primed in the presence of HIV-1 suppressed priming of other naïve T cells in a contact-dependent manner. We identified PD-1, CTLA-4, and TRAIL pathways as responsible for this suppresion, as blocking these negative molecules restored T-cell proliferation to a higher degree. In conclusion, the presence of HIV-1 during DC priming produced cells with inhibitory effects on T-cell activation and proliferation, i.e. suppressor T cells, a mechanism that could contribute to the enhancement of HIV-1 pathogenesis.
authors.affiliation: Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. karlhans.fru.che@liu.se
authors.forename: Karlhans F
authors.initials: KF
authors.lastname: Che
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Sabado
authors.forename: Esaki M
authors.initials: EM
authors.lastname: Shankar
authors.forename: Veronica
authors.initials: V
authors.lastname: Tjomsland
authors.forename: Davorka
authors.initials: D
authors.lastname: Messmer
authors.forename: Nina
authors.initials: N
authors.lastname: Bhardwaj
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000737:chemistry; D019138:Antibodies, Blocking / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen; D002450:Cell Communication; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D004220:Disulfides / Q000737:chemistry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015488:HIV Antigens / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D061026:Programmed Cell Death 1 Receptor; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D004220:Disulfides; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015488:HIV Antigens; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D053221:TNF-Related Apoptosis-Inducing Ligand; C001105:2,2'-dipyridyl disulfide; D015082:2,2'-Dipyridyl
references.citation: J Immunol. 2005 Oct 1;175(7):4566-74
references.pmid: 16177101
references.citation: Eur J Immunol. 2002 Mar;32(3):634-43
references.pmid: 11857337
references.citation: J Immunol. 2002 May 15;168(10):4881-8
references.pmid: 11994437
references.citation: Cell. 2000 Mar 3;100(5):575-85
references.pmid: 10721994
references.citation: Cell. 2008 May 30;133(5):775-87
references.pmid: 18510923
references.citation: Nat Med. 2006 Oct;12(10):1198-202
references.pmid: 16917489
references.citation: Nat Immunol. 2002 Oct;3(10):975-83
references.pmid: 12352970
references.citation: J Exp Med. 2004 Nov 15;200(10):1279-88
references.pmid: 15545354
references.citation: FASEB J. 2004 Sep;18(12):1459-61
references.pmid: 15240562
references.citation: Int Immunol. 2005 Feb;17(2):103-16
references.pmid: 15611322
references.citation: Nat Immunol. 2007 Nov;8(11):1246-54
references.pmid: 17906628
references.citation: Nat Rev Immunol. 2003 Nov;3(11):867-78
references.pmid: 14668803
references.citation: Curr Drug Targets. 2006 Dec;7(12):1563-9
references.pmid: 17168831
references.citation: Nat Rev Immunol. 2008 Jul;8(7):523-32
references.pmid: 18566595
references.citation: Blood. 2004 Nov 15;104(10):3249-56
references.pmid: 15271794
references.citation: Nat Med. 2007 Oct;13(10):1155-9
references.pmid: 17917664
references.citation: AIDS. 2002 Jan 25;16(2):171-80
references.pmid: 11807300
references.citation: J Infect Dis. 2003 Jan 1;187(1):26-37
references.pmid: 12508143
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3390-5
references.pmid: 17360656
references.citation: Curr Mol Med. 2003 May;3(3):265-72
references.pmid: 12699362
references.citation: Trends Mol Med. 2007 Mar;13(3):108-16
references.pmid: 17257897
references.citation: Expert Rev Vaccines. 2008 Mar;7(2):155-8
references.pmid: 18324885
references.citation: J Virol. 1998 Oct;72(10):7992-8001
references.pmid: 9733838
references.citation: Front Biosci. 2008 Jan 01;13:1152-70
references.pmid: 17981620
references.citation: Science. 1997 Apr 4;276(5309):111-3
references.pmid: 9082980
references.citation: Nat Med. 2003 Feb;9(2):191-7
references.pmid: 12539042
references.citation: Proc Natl Acad Sci U S A. 2004 May 18;101(20):7669-74
references.pmid: 15128934
references.citation: Nature. 2006 Sep 21;443(7109):350-4
references.pmid: 16921384
references.citation: Curr Opin Immunol. 2007 Jun;19(3):309-14
references.pmid: 17433872
references.citation: J Virol. 2004 May;78(10):5223-32
references.pmid: 15113904
references.citation: Annu Rev Immunol. 2005;23:515-48
references.pmid: 15771580
references.citation: Blood. 2007 Jun 1;109(11):4671-8
references.pmid: 17272504
references.citation: Blood. 2005 Mar 15;105(6):2458-64
references.pmid: 15585654
references.citation: J Exp Med. 1996 Jun 1;183(6):2541-50
references.pmid: 8676075
references.citation: J Virol. 1993 Apr;67(4):2182-90
references.pmid: 8445728
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):19079-84
references.pmid: 18025463
references.citation: Blood. 2001 Nov 15;98(10):3016-21
references.pmid: 11698285
references.citation: Endocrinology. 2009 Apr;150(4):2000-7
references.pmid: 19008314
references.citation: PLoS One. 2009;4(1):e4256
references.pmid: 19165342
references.citation: Cell Death Differ. 2007 Dec;14(12):2076-84
references.pmid: 17762882
references.citation: Nat Rev Immunol. 2003 Mar;3(3):253-7
references.pmid: 12658273
references.citation: Blood. 2004 Nov 1;104(9):2810-7
references.pmid: 15231570
references.citation: Trends Immunol. 2007 May;28(5):227-33
references.pmid: 17403614
references.citation: J Virol. 2007 Sep;81(17):9249-58
references.pmid: 17567698
references.citation: AIDS Res Hum Retroviruses. 2001 Jan 20;17(2):99-104
references.pmid: 11177389
references.citation: AIDS. 2002 Jul 5;16(10):1319-29
references.pmid: 12131208