title: Contribution of herpesvirus specific CD8 T cells to anti-viral T cell response in humans.
abstract: Herpesviruses infect most humans. Their infections can be associated with pathological conditions and significant changes in T cell repertoire but evidences of symbiotic effects of herpesvirus latency have never been demonstrated. We tested the hypothesis that HCMV and EBV-specific CD8 T cells contribute to the heterologous anti-viral immune response. Volume of activated/proliferating virus-specific and total CD8 T cells was evaluated in 50 patients with acute viral infections: 20 with HBV, 12 with Dengue, 12 with Influenza, 3 with Adenovirus infection and 3 with fevers of unknown etiology. Virus-specific (EBV, HCMV, Influenza) pentamer+ and total CD8 T cells were analyzed for activation (CD38/HLA-DR), proliferation (Ki-67/Bcl-2(low)) and cytokine production. We observed that all acute viral infections trigger an expansion of activated/proliferating CD8 T cells, which differs in size depending on the infection but is invariably inflated by CD8 T cells specific for persistent herpesviruses (HCMV/EBV). CD8 T cells specific for other non-related non persistent viral infection (i.e. Influenza) were not activated. IL-15, which is produced during acute viral infections, is the likely contributing mechanism driving the selective activation of herpesvirus specific CD8 T cells. In addition we were able to show that herpesvirus specific CD8 T cells displayed an increased ability to produce the anti-viral cytokine interferon-gamma during the acute phase of heterologous viral infection. Taken together, these data demonstrated that activated herpesvirus specific CD8 T cells inflate the activated/proliferating CD8 T cells population present during acute viral infections in human and can contribute to the heterologous anti-viral T cell response.
authors.affiliation: Singapore Institute for Clinical Sciences, A*STAR, Singapore.
authors.forename: Elena
authors.initials: E
authors.lastname: Sandalova
authors.forename: Diletta
authors.initials: D
authors.lastname: Laccabue
authors.forename: Carolina
authors.initials: C
authors.lastname: Boni
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Tan
authors.forename: Katja
authors.initials: K
authors.lastname: Fink
authors.forename: Eng Eong
authors.initials: EE
authors.lastname: Ooi
authors.forename: Robert
authors.initials: R
authors.lastname: Chua
authors.forename: Bahar
authors.initials: B
authors.lastname: Shafaeddin Schreve
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrari
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertoletti
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006564:Herpesviridae / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D010641:Phenotype; D014777:Virus Diseases / Q000276:immunology*; D055815:Young Adult
references.citation: Immunity. 1999 Dec;11(6):733-42
references.pmid: 10626895
references.citation: Hepatology. 2000 Nov;32(5):1117-24
references.pmid: 11050064
references.citation: Clin Microbiol Rev. 2009 Jan;22(1):76-98, Table of Contents
references.pmid: 19136435
references.citation: Gastroenterology. 2009 Oct;137(4):1289-300
references.pmid: 19591831
references.citation: J Immunol. 2004 Aug 15;173(4):2410-8
references.pmid: 15294954
references.citation: Immunity. 1998 Oct;9(4):459-66
references.pmid: 9806632
references.citation: Nat Rev Cancer. 2004 Oct;4(10):757-68
references.pmid: 15510157
references.citation: J Clin Microbiol. 2007 Mar;45(3):935-41
references.pmid: 17215345
references.citation: J Gen Virol. 2006 Jun;87(Pt 6):1439-1449
references.pmid: 16690908
references.citation: J Virol. 1999 Mar;73(3):2099-108
references.pmid: 9971792
references.citation: J Immunol. 2008 Sep 15;181(6):3741-4
references.pmid: 18768824
references.citation: Transplantation. 2004 Jan 15;77(1):76-84
references.pmid: 14724439
references.citation: J Immunol. 2002 Nov 15;169(10):5838-43
references.pmid: 12421965
references.citation: J Immunol Methods. 2002 Oct 1;268(1):9-19
references.pmid: 12213338
references.citation: J Immunol. 2007 Aug 1;179(3):1988-95
references.pmid: 17641066
references.citation: Philos Trans R Soc Lond B Biol Sci. 2000 Mar 29;355(1395):317-22
references.pmid: 10794049
references.citation: J Immunol. 2003 Feb 15;170(4):2022-9
references.pmid: 12574372
references.citation: J Immunol. 1999 Feb 1;162(3):1827-35
references.pmid: 9973448
references.citation: Nature. 2007 May 17;447(7142):326-9
references.pmid: 17507983
references.citation: J Immunol. 2003 Oct 15;171(8):4352-8
references.pmid: 14530360
references.citation: J Allergy Clin Immunol. 2006 May;117(5):969-77; quiz 978
references.pmid: 16675321
references.citation: J Virol. 2000 Sep;74(17):8140-50
references.pmid: 10933725
references.citation: Nat Immunol. 2001 Nov;2(11):1067-76
references.pmid: 11668342
references.citation: Eur J Immunol. 2006 Sep;36(9):2347-58
references.pmid: 16909431
references.citation: J Exp Med. 1998 Nov 2;188(9):1705-15
references.pmid: 9802982
references.citation: J Exp Med. 1998 Sep 21;188(6):1047-54
references.pmid: 9743523
references.citation: J Immunol Methods. 2002 Oct 1;268(1):21-8
references.pmid: 12213339
references.citation: J Immunol. 2003 Apr 15;170(8):4342-8
references.pmid: 12682271
references.citation: J Exp Med. 2005 Sep 5;202(5):673-85
references.pmid: 16147978
references.citation: Blood. 2006 Nov 1;108(9):2942-9
references.pmid: 16835376
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6192-7
references.pmid: 11972069
references.citation: Nat Med. 2002 Apr;8(4):379-85
references.pmid: 11927944
references.citation: J Immunol. 2004 Dec 15;173(12):7481-9
references.pmid: 15585874
references.citation: J Immunol. 2004 May 15;172(10):6107-14
references.pmid: 15128796
references.citation: Immunity. 2008 May;28(5):710-22
references.pmid: 18468462
references.citation: J Immunol. 1995 Nov 15;155(10):5046-56
references.pmid: 7594513
references.citation: J Exp Med. 2003 Nov 17;198(10):1583-93
references.pmid: 14623912
references.citation: Nat Rev Immunol. 2002 Jun;2(6):417-26
references.pmid: 12093008
references.citation: PLoS Biol. 2004 Feb;2(2):E20
references.pmid: 14966528