Predominance of heterosubtypic IFN-γ-only-secreting effector memory T cells in pandemic H1N1 naive adults.
The 2009/10 pandemic (pH1N1) highlighted the need for vaccines conferring heterosubtypic immunity against antigenically shifted influenza strains. Although cross-reactive T cells are strong candidates for mediating heterosubtypic immunity, little is known about the population-level prevalence, frequency, and cytokine-secretion profile of heterosubtypic T cells to pH1N1. To assess this, pH1N1 sero-negative adults were recruited. Single-cell IFN-γ and IL-2 cytokine-secretion profiles to internal proteins of pH1N1 or live virus were enumerated and characterised. Heterosubtypic T cells recognising pH1N1 core proteins were widely prevalent, being detected in 90% (30 of 33) of pH1N1-naïve individuals. Although the last exposure to influenza was greater than 6 months ago, the frequency and proportion of the IFN-γ-only-secreting T-cell subset was significantly higher than the IL-2-only-secreting subset. CD8(+) IFN-γ-only-secreting heterosubtypic T cells were predominantly CCR7(-) CD45RA(-) effector-memory phenotype, expressing the tissue-homing receptor CXCR3 and degranulation marker CD107. Receipt of the 2008-09 influenza vaccine did not alter the frequency of these heterosubtypic T cells, highlighting the inability of current vaccines to maintain this heterosubtypic T-cell pool. The surprisingly high prevalence of pre-existing circulating pH1N1-specific CD8(+) IFN-γ-only-secreting effector memory T cells with cytotoxic and lung-homing potential in pH1N1-seronegative adults may partly explain the low case fatality rate despite high rates of infection of the pandemic in young adults.
Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, Paddington, London, UK. s.sridhar@imperial.ac.uk
Saranya
S
Sridhar
Shaima
S
Begom
Alison
A
Bermingham
Thedi
T
Ziegler
Kim L
KL
Roberts
Wendy S
WS
Barclay
Peter
P
Openshaw
Ajit
A
Lalvani
D000293:Adolescent; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015331:Cohort Studies; D003429:Cross Reactions / Q000276:immunology; D005434:Flow Cytometry; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D007371:Interferon-gamma / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology; D007963:Leukocytes, Mononuclear; D008875:Middle Aged; D058873:Pandemics; D015995:Prevalence; D055815:Young Adult
D000914:Antibodies, Viral; D007376:Interleukin-2; D007371:Interferon-gamma