CD8+ T cell immunity to 2009 pandemic and seasonal H1N1 influenza viruses

Abstract

A novel strain of H1N1 influenza A virus (pH1N1) emerged in 2009, causing a worldwide pandemic. Several studies suggest that this virus is antigenically more closely related to human influenza viruses that circulated prior to 1957 than viruses of more recent seasonal influenza varieties. The extent to which individuals who are naïve to the 2009 pH1N1 virus carry cross-reactive CD8+ T cells is not known, but a certain degree of reactivity would be expected since there is substantial conservation among the internal proteins of the virus. In the present study, we examined production of multiple cytokines in response to virus from CD8+ T cells in healthy adult subjects, between 18 and 50 years of age (born post 1957), who had no evidence of exposure to the 2009 pH1N1 virus, and had blood collected prior to the emergence of the pandemic in April of 2009. Human peripheral blood mononuclear cells (PBMC) were stimulated in vitro with a panel of live viruses, and assayed by intracellular cytokine staining and flow cytometry. Although results were variable, most subjects exhibited cytokine positive CD8+ T cells in response to pH1N1. Cytokine producing cells were predominantly single positive (IL2, IFNγ, or TNFα); triple-cytokine producing cells were relatively rare. This result suggests that although many adults carry cross-reactive T cells against the emergent pandemic virus, these cells are in a functionally limited state, possibly because these subjects have not had recent exposure to either seasonal or pandemic influenza strains.

Infection with Seasonal Influenza Virus Elicits CD4 T Cells Specific for Genetically Conserved Epitopes That Can Be Rapidly Mobilized for Protective Immunity to Pandemic H1N1 Influenza Virus

“…Depending on the study and region analyzed, individuals under the age of 25 years represented 45% to 60% of infected subjects, though the pathogenic effects of H1N1 virus infection were most pronounced in individuals more than 60 years old (4,36). These findings, as well as recent immunological studies from our laboratory and other laboratories (11,17,20,22,25,33,39,48,51,52,55,61,62), suggest that previous encounters with vaccines or viruses provide immunological advantages and immunological memory in the population despite the "serological distance" between the hemagglutinin (HA) and neuraminidase (NA) proteins of seasonal and pandemic strains.…”

Memory CD8+T Cells Are Sufficient To Alleviate Impaired Host Resistance to Influenza A Virus Infection Caused by Neonatal Oxygen Supplementation

“…The recent emergence of the 2009 pandemic influenza (H1N1) and avian influenza (H5N1) viruses has triggered a renewed interest in elements that confer immune protection across multiple strains of influenza virus. Multiple groups have reported that seasonal influenza vaccination can generate CD8 ϩ T cells that cross-react against pandemic and avian influenza virus antigens (26,34,38). In a mouse model, adoptive transfer of influenza virus H3N2-specific T cells can confer protection against the 2009 H1N1 influenza virus (17).…”

Antibody-Dependent Cellular Cytotoxicity Is Associated with Control of Pandemic H1N1 Influenza Virus Infection of Macaques

“…There is circumstantial evidence from human studies and animal models that T cells recognizing conserved epitopes can mediate heterotypic immunity against divergent influenza virus strains in the absence of crossreactive NAbs (15)(16)(17)(18)(19)(20)(21)(22), though this concept has so far been tested directly only in mice (21). Accordingly, a number of studies have suggested that infection with seasonal influenza virus provides a level of protection against the swine-origin pandemic 2009 influenza virus (H1N1pdm) in the absence of NAbs, an effect which may be mediated by cross-reactive T cell responses (17,(23)(24)(25)(26)(27)(28). However, the degree to which T cells can mediate effective, longlived heterotypic immunity to influenza in humans remains unclear.…”