Cellular immune correlates of protection against symptomatic pandemic influenza

Nat Med. 2013 Oct;19(10):1305-12. doi: 10.1038/nm.3350. Epub 2013 Sep 22.

Abstract

The role of T cells in mediating heterosubtypic protection against natural influenza illness in humans is uncertain. The 2009 H1N1 pandemic (pH1N1) provided a unique natural experiment to determine whether crossreactive cellular immunity limits symptomatic illness in antibody-naive individuals. We followed 342 healthy adults through the UK pandemic waves and correlated the responses of pre-existing T cells to the pH1N1 virus and conserved core protein epitopes with clinical outcomes after incident pH1N1 infection. Higher frequencies of pre-existing T cells to conserved CD8 epitopes were found in individuals who developed less severe illness, with total symptom score having the strongest inverse correlation with the frequency of interferon-γ (IFN-γ)(+) interleukin-2 (IL-2)(-) CD8(+) T cells (r = -0.6, P = 0.004). Within this functional CD8(+)IFN-γ(+)IL-2(-) population, cells with the CD45RA(+) chemokine (C-C) receptor 7 (CCR7)(-) phenotype inversely correlated with symptom score and had lung-homing and cytotoxic potential. In the absence of crossreactive neutralizing antibodies, CD8(+) T cells specific to conserved viral epitopes correlated with crossprotection against symptomatic influenza. This protective immune correlate could guide universal influenza vaccine development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD8-Positive T-Lymphocytes / immunology
  • Cohort Studies
  • Cross Reactions
  • Humans
  • Immunity, Cellular*
  • Immunologic Memory
  • Immunophenotyping
  • Influenza A Virus, H1N1 Subtype / isolation & purification
  • Influenza, Human / epidemiology
  • Influenza, Human / immunology*
  • Influenza, Human / physiopathology
  • Influenza, Human / virology
  • Severity of Illness Index
  • United Kingdom / epidemiology
  • Virus Shedding