Human T-cells directed to seasonal influenza A virus cross-react with 2009 pandemic influenza A (H1N1) and swine-origin triple-reassortant H3N2 influenza viruses

Abstract

Virus-specific CD8 + T-cells contribute to protective immunity against influenza A virus (IAV) infections. As the majority of these cells are directed to conserved viral proteins, they may afford protection against IAVs of various subtypes. The present study assessed the cross-reactivity of human CD8 + T-lymphocytes, induced by infection with seasonal A (H1N1) or A (H3N2) influenza virus, with 2009 pandemic influenza A (H1N1) virus [A(H1N1)pdm09] and swine-origin triplereassortant A (H3N2) [A(H3N2)v] viruses that are currently causing an increasing number of human cases in the USA. It was demonstrated that CD8 + T-cells induced after seasonal IAV infections exerted lytic activity and produced gamma interferon upon in vitro restimulation with A(H1N1)pdm09 and A(H3N2)v influenza A viruses. Furthermore, CD8 + T-cells directed to A(H1N1)pdm09 virus displayed a high degree of cross-reactivity with A(H3N2)v viruses. It was concluded that cross-reacting T-cells had the potential to afford protective immunity against A(H1N1)pdm09 viruses during the pandemic and offer some degree of protection against infection with A(H3N2)v viruses.

Human Cytotoxic T Lymphocytes Directed to Seasonal Influenza A Viruses Cross-React with the Newly Emerging H7N9 Virus

“…1E). As for the other subjects, no cross-reactivity was observed with the H7N9 variant of the NP [44][45][46][47][48][49][50][51][52] (CTELKL SDN) epitope with CD8 ϩ T cells obtained from subject 5. Overall, the extent of cross-reactivity of influenza virus-specific CD8 ϩ T cells against individual H7N9 variant epitopes was low and dependent on the study subjects and peptides tested.…”

“…On the other hand, virus-specific CD8 ϩ T cells (cytotoxic T lymphocytes [CTLs]), induced after infection with seasonal influenza A viruses, are mainly directed to the conserved internal proteins of influenza A viruses (33,(42)(43)(44)(45)(46)(47)(48)(49)(50)(51). The presence of these cross-reactive CD8 ϩ T cells may afford a certain degree of heterosubtypic immunity against infection with novel H7N9 viruses.…”

“…Using various combinations of influenza A virus subtypes for pri-mary and secondary infection, this type of immunity and the contribution of virus-specific CD8 ϩ T cells were demonstrated in various animal models (52)(53)(54)(55)(56)(57). Evidence for heterosubtypic immunity and the role of CD8 ϩ T cells in humans is limited (58)(59)(60)(61), though the presence of CD8 ϩ T cells cross-reactive with avian H5N1 and swine origin triple-reassortant A H3N2 (vH3N2) viruses has been demonstrated (49)(50)(51)62). It is unknown to what extent CD8 ϩ T cells elicited by a seasonal or 2009 pH1N1 influenza A virus infection cross-react with the novel H7N9 virus.…”

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“…The cross-protective immune response is possible if the epitopes of the conservative influenza virus proteins that are known to be predominantly recognized by the T-lymphocytes (CD4 + and CD8 + ) are presented effectively [28]. As was shown in animal models, the cell immune response might have a protective role in case of homological and heterological infections [29][30][31][32][33][34][35]. The results of the adaptive transfer of T-cells from the primed mice to the naive recipients prove the protective function of the CD4 + and CD8 + cells [36].…”

In vitro modeling of the interaction between human epithelial cells and lymphocytes upon influenza infection

“…Influenza virions infect the cells of respiratory pseudostratified columnar epithelium consisting of a single layer of three major cells types, namely ciliated, goblet, and Clara cells 2. Data from murine studies, along with limited human data, suggest that CD8 + cytotoxic T lymphocytes (CTL) that recognize conserved epitopes of structural influenza proteins are the main mediators of influenza virus clearance 3, 4, 5, 6, 7. Additionally, the fact that many CTLs recognize epitopes shared between different influenza strains offers the potential for broad cross‐strain immunity 8, 9, 10.…”