title: Avidity of influenza-specific memory CD8+ T-cell populations decays over time compromising antiviral immunity.
abstract: Decline of cell-mediated immunity is often attributed to decaying T-cell numbers and their distribution in peripheral organs. This study examined the hypothesis that qualitative as well as quantitative changes contribute to the declining efficacy of CD8(+)  T-cell memory. Using a model of influenza virus infection, where loss of protective CD8(+)  T-cell immunity was observed 6 months postinfection, we found no decline in antigen-specific T-cell numbers or migration to the site of secondary infection. There was, however, a large reduction in antigen-specific CD8(+)  T-cell degranulation, cytokine secretion, and polyfunctionality. A profound loss of high-avidity T cells over time indicated that failure to confer protective immunity resulted from the inferior functional capacity of remaining low avidity cells. These data imply that high-avidity central memory T cells wane with declining antigen levels, leaving lower avidity T cells with reduced functional capabilities.
authors.affiliation: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK. humphreysir@cardiff.ac.uk
authors.forename: Ian R
authors.initials: IR
authors.lastname: Humphreys
authors.forename: Mathew
authors.initials: M
authors.lastname: Clement
authors.forename: Morgan
authors.initials: M
authors.lastname: Marsden
authors.forename: Kristin
authors.initials: K
authors.lastname: Ladell
authors.forename: James E
authors.initials: JE
authors.lastname: McLaren
authors.forename: Kathryn
authors.initials: K
authors.lastname: Smart
authors.forename: James P
authors.initials: JP
authors.lastname: Hindley
authors.forename: Hayley M
authors.initials: HM
authors.lastname: Bridgeman
authors.forename: Hugo A
authors.initials: HA
authors.lastname: van den Berg
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Ann
authors.initials: A
authors.lastname: Ager
authors.forename: Linda
authors.initials: L
authors.lastname: Wooldridge
authors.forename: Andrew
authors.initials: A
authors.lastname: Godkin
authors.forename: Awen M
authors.initials: AM
authors.lastname: Gallimore
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes; D015550:Cell Degranulation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D007111:Immunity, Cellular; D007156:Immunologic Memory; D029521:Alphainfluenzavirus / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D016207:Cytokines