title: Influenza-specific T cells from older people are enriched in the late effector subset and their presence inversely correlates with vaccine response.
abstract: T cells specific for persistent pathogens accumulate with age and express markers of immune senescence. In contrast, much less is known about the state of T cell memory for acutely infecting pathogens. Here we examined T cell responses to influenza in human peripheral blood mononuclear cells from older (>64) and younger (<40) donors using whole virus restimulation with influenza A (A/PR8/34) ex vivo. Although most donors had pre-existing influenza reactive T cells as measured by IFNγ production, older donors had smaller populations of influenza-responsive T cells than young controls and had lost a significant proportion of their CD45RA-negative functional memory population. Despite this apparent dysfunction in a proportion of the older T cells, both old and young donors' T cells from 2008 could respond to A/California/07/2009 ex vivo. For HLA-A2+ donors, MHC tetramer staining showed that a higher proportion of influenza-specific memory CD8 T cells from the 65+ group co-express the markers killer cell lectin-like receptor G1 (KLRG1) and CD57 compared to their younger counterparts. These markers have previously been associated with a late differentiation state or immune senescence. Thus, memory CD8 T cells to an acutely infecting pathogen show signs of advanced differentiation and functional deterioration with age. There was a significant negative correlation between the frequency of KLRG1(+)CD57(+) influenza M1-specific CD8 T cells pre-vaccination and the ability to make antibodies in response to vaccination with seasonal trivalent inactivated vaccine, whereas no such trend was observed when the total CD8(+)KLRG1(+)CD57(+) population was analyzed. These results suggest that the state of the influenza-specific memory CD8 T cells may be a predictive indicator of a vaccine responsive healthy immune system in old age.
authors: Department of Immunology, University of Toronto, Toronto, Canada.
authors: Lisa E
authors: LE
authors: Wagar
authors: Beth
authors: B
authors: Gentleman
authors: Hanspeter
authors: H
authors: Pircher
authors: Janet E
authors: JE
authors: McElhaney
authors: Tania H
authors: TH
authors: Watts
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001769:Blood / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D007156:Immunologic Memory / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology* / Q000494:pharmacology; D007251:Influenza, Human / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D007252:Influenza Vaccines