title: Telomere Length as an Indicator of the Robustness of B- and T-Cell Response to Influenza in Older Adults.
abstract: BACKGROUND
  Telomeres provide a key mechanism for protecting the integrity of chromosomes and their attrition after cell division and during aging are evident in lymphocytes. However, the significance of telomere shortening in age-associated decline of immune function is unknown.
  
  
  METHODS
  We selected 22 HLA-A2-positive healthy older adults who have relatively short or long telomere lengths to compare their antibody response against the influenza vaccine, and their CD8(+) T-cell response against an influenza antigen.
  
  
  RESULTS
  B cells from individuals with a robust antibody response to the influenza vaccine had significantly longer telomeres than those with a poor antibody response. Monocyte-derived antigen-presenting cells of both short and long telomere groups induced similar expansions of influenza M1-specific CD8(+) T cells. Vaccination did not increase M1-specific CD8(+) T cells in blood, but M1-specific CD8(+) T cells from the long telomere group exhibited significantly greater expansion in vitro than those from the short telomere group. Finally, M1-specific CD8(+) T cells that underwent more expansions had significantly longer telomeres than cells with fewer divisions.
  
  
  CONCLUSIONS
  Telomere length is positively associated with a robust lymphocyte response, and telomere attrition may contribute to the age-associated decline of adaptive immunity.
authors.affiliation: Laboratory of Molecular Biology and Immunology.
authors.forename: Kevin
authors.initials: K
authors.lastname: Najarro
authors.affiliation: Laboratory of Molecular Biology and Immunology.
authors.forename: Huy
authors.initials: H
authors.lastname: Nguyen
authors.affiliation: Laboratory of Molecular Biology and Immunology.
authors.forename: Guobing
authors.initials: G
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular Biology and Immunology.
authors.forename: Mai
authors.initials: M
authors.lastname: Xu
authors.affiliation: Translational Gerontology Branch.
authors.forename: Sandy
authors.initials: S
authors.lastname: Alcorta
authors.affiliation: Departments of Medicine.
authors.forename: Xu
authors.initials: X
authors.lastname: Yao
authors.affiliation: Translational Gerontology Branch.
authors.forename: Linda
authors.initials: L
authors.lastname: Zukley
authors.affiliation: Translational Gerontology Branch.
authors.forename: E Jeffrey
authors.initials: EJ
authors.lastname: Metter
authors.affiliation: Laboratory of Molecular Biology and Immunology.
authors.forename: Thai
authors.initials: T
authors.lastname: Truong
authors.affiliation: Laboratory of Molecular Biology and Immunology.
authors.forename: Yun
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Departments of Medicine.
authors.forename: Huifen
authors.initials: H
authors.lastname: Li
authors.affiliation: Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Mathias
authors.initials: M
authors.lastname: Oelke
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Xiyan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Translational Gerontology Branch.
authors.forename: Shari M
authors.initials: SM
authors.lastname: Ling
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
authors.forename: Dan L
authors.initials: DL
authors.lastname: Longo
authors.affiliation: Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Schneck
authors.affiliation: Departments of Medicine.
authors.forename: Sean
authors.initials: S
authors.lastname: Leng
authors.affiliation: Translational Gerontology Branch.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: Laboratory of Molecular Biology and Immunology.
authors.forename: Nan-ping
authors.initials: NP
authors.lastname: Weng
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D008297:Male; D059506:Telomere Shortening / Q000276:immunology*
chemical_list: D015789:HLA-A2 Antigen; D007252:Influenza Vaccines
keywords: CD28− T cells; CD8 T cells; CMV; antibody; influenza vaccine; telomere
references.citation: Curr Protoc Immunol. 2004 Sep;Chapter 10:10.30.1-10.30.27
references.pmid: 18432920
references.citation: J Immunol. 2010 May 1;184(9):5151-9
references.pmid: 20368274
references.citation: Nucleic Acids Res. 2002 May 15;30(10):e47
references.pmid: 12000852
references.citation: J Immunol. 2000 Aug 1;165(3):1191-6
references.pmid: 10903716
references.citation: Ageing Res Rev. 2011 Jul;10(3):379-88
references.pmid: 21055484
references.citation: J Virol. 2001 Dec;75(24):12182-7
references.pmid: 11711609
references.citation: Annu Rev Genomics Hum Genet. 2009;10:45-61
references.pmid: 19405848
references.citation: Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10114-8
references.pmid: 1438199
references.citation: Exp Gerontol. 2013 Jun;48(6):579-86
references.pmid: 23473930
references.citation: Curr Biol. 1998 Feb 26;8(5):R178-81
references.pmid: 9501064
references.citation: J Immunol. 1996 May 15;156(10):3587-90
references.pmid: 8621891
references.citation: Curr Opin Immunol. 2013 Aug;25(4):504-10
references.pmid: 23932400
references.citation: Clin Vaccine Immunol. 2009 Jul;16(7):1066-73
references.pmid: 19494085
references.citation: Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10827-32
references.pmid: 9380719
references.citation: Curr Opin Immunol. 2012 Aug;24(4):470-5
references.pmid: 22626625
references.citation: Nature. 2011 May 22;474(7351):399-402
references.pmid: 21602826
references.citation: Exp Gerontol. 1994 Nov-Dec;29(6):601-9
references.pmid: 9435913
references.citation: Nat Rev Immunol. 2002 Dec;2(12):982-7
references.pmid: 12461571
references.citation: J Exp Med. 1999 Jul 19;190(2):157-67
references.pmid: 10432279
references.citation: J Clin Immunol. 2003 Jul;23(4):247-57
references.pmid: 12959217
references.citation: J Infect Dis. 2008 Nov 1;198(9):1353-7
references.pmid: 18816191
references.citation: J Immunol. 2010 Apr 1;184(7):3417-23
references.pmid: 20176738
references.citation: J Immunol. 2002 Jun 1;168(11):5893-9
references.pmid: 12023394
references.citation: Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11190-4
references.pmid: 7479963
references.citation: J Clin Invest. 2011 Aug;121(8):3109-19
references.pmid: 21785218
references.citation: J Immunol. 2014 Oct 1;193(7):3624-31
references.pmid: 25187662
references.citation: Nat Immunol. 2013 May;14(5):428-36
references.pmid: 23598398
references.citation: AIDS. 1996 Jul;10(8):F17-22
references.pmid: 8828735
references.citation: Genes Dev. 2005 Sep 15;19(18):2100-10
references.pmid: 16166375
references.citation: Mech Ageing Dev. 2000 Nov 15;119(3):89-99
references.pmid: 11080530
references.citation: Biochim Biophys Acta. 2009 Apr;1792(4):371-9
references.pmid: 19419704
references.citation: Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11091-4
references.pmid: 7479943
references.citation: Pediatr Res. 2002 Sep;52(3):377-81
references.pmid: 12193671
references.citation: Mech Ageing Dev. 2008 Jan-Feb;129(1-2):60-6
references.pmid: 18199471
references.citation: Cancer Genet Cytogenet. 1998 Sep;105(2):138-44
references.pmid: 9723031
references.citation: Vaccine. 2011 Jul 12;29(31):5015-21
references.pmid: 21565245
references.citation: Clin Sci (Lond). 2015 Mar;128(6):367-77
references.pmid: 25317735
references.citation: Blood. 1996 Jul 1;88(1):222-9
references.pmid: 8704177
references.citation: Vaccine. 2012 Mar 9;30(12):2060-7
references.pmid: 22289511
references.citation: Genet Med. 2010 Dec;12(12):753-64
references.pmid: 21189492
references.citation: Immunity. 2006 May;24(5):495-9
references.pmid: 16713964
references.citation: Aging (Albany NY). 2010 Nov;2(11):867-74
references.pmid: 21113082
references.citation: Nature. 2000 Nov 2;408(6808):53-6
references.pmid: 11081503
references.citation: Nat Rev Immunol. 2002 Sep;2(9):699-706
references.pmid: 12209138
references.citation: Nature. 1990 May 31;345(6274):458-60
references.pmid: 2342578