title: Age-associated increase of low-avidity cytomegalovirus-specific CD8+ T cells that re-express CD45RA.
abstract: The mechanisms regulating memory CD8(+) T cell function and homeostasis during aging are unclear. CD8(+) effector memory T cells that re-express CD45RA increase considerably in older humans and both aging and persistent CMV infection are independent factors in this process. We used MHC class I tetrameric complexes that were mutated in the CD8 binding domain to identify CMV-specific CD8(+) T cells with high Ag-binding avidity. In individuals who were HLA-A*0201, CD8(+) T cells that expressed CD45RA and were specific for the pp65 protein (NLVPMVATV epitope) had lower avidity than those that expressed CD45RO and demonstrated decreased cytokine secretion and cytolytic potential after specific activation. Furthermore, low avidity NLVPMVATV-specific CD8(+) T cells were significantly increased in older individuals. The stimulation of blood leukocytes with CMV lysate induced high levels of IFN-α that in turn induced IL-15 production. Moreover, the addition of IL-15 to CD45RA(-)CD45RO(+) CMV-specific CD8(+) T cells induced CD45RA expression while Ag activated cells remained CD45RO(+). This raises the possibility that non-specific cytokine-driven accumulation of CMV-specific CD8(+)CD45RA(+) T cells with lower Ag-binding avidity may exacerbate the effects of viral reactivation on skewing the T cell repertoire in CMV-infected individuals during aging.
authors: Division of Infection and Immunity, University College London, London WC1E 6BT, United Kingdom.
authors: Stephen J
authors: SJ
authors: Griffiths
authors: Natalie E
authors: NE
authors: Riddell
authors: Joanne
authors: J
authors: Masters
authors: Valentina
authors: V
authors: Libri
authors: Sian M
authors: SM
authors: Henson
authors: Anne
authors: A
authors: Wertheimer
authors: Diana
authors: D
authors: Wallace
authors: Stuart
authors: S
authors: Sims
authors: Laura
authors: L
authors: Rivino
authors: Anis
authors: A
authors: Larbi
authors: David M
authors: DM
authors: Kemeny
authors: Janko
authors: J
authors: Nikolich-Zugich
authors: Florian
authors: F
authors: Kern
authors: Paul
authors: P
authors: Klenerman
authors: Vince C
authors: VC
authors: Emery
authors: Arne N
authors: AN
authors: Akbar
mesh_terms: D000367:Age Factors; D000915:Antibody Affinity / Q000276:immunology; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000096:biosynthesis; D019409:Interleukin-15 / Q000276:immunology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010750:Phosphoproteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D000941:Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D016898:Interferon-alpha; D019409:Interleukin-15; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D017493:Leukocyte Common Antigens
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