Influenza-specific T cells from older people are enriched in the late effector subset and their presence inversely correlates with vaccine response

PLoS One. 2011;6(8):e23698. doi: 10.1371/journal.pone.0023698. Epub 2011 Aug 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Blood / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • Humans
  • Immunity, Humoral / drug effects
  • Immunologic Memory / immunology
  • Influenza Vaccines / immunology*
  • Influenza Vaccines / pharmacology
  • Influenza, Human / immunology
  • T-Cell Antigen Receptor Specificity / immunology*
  • T-Lymphocytes / immunology*

Substances

  • Influenza Vaccines