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.
Original language | English |
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Pages (from-to) | 1305-12 |
Number of pages | 8 |
Journal | Nature Medicine |
Volume | 19 |
Issue number | 10 |
DOIs | |
Publication status | Published - Oct 2013 |
Keywords
- Adult
- CD8-Positive T-Lymphocytes
- Cohort Studies
- Cross Reactions
- Great Britain
- Humans
- Immunity, Cellular
- Immunologic Memory
- Immunophenotyping
- Influenza A Virus, H1N1 Subtype
- Influenza, Human
- Severity of Illness Index
- Virus Shedding