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Type of publication: Journal Article
Type of document: Full Paper

Year: 2016

Authors: Talker, SC; Stadler, M; Koinig, HC; Mair, KH; Rodríguez-Gómez, IM; Graage, R; Zell, R; Dürrwald, R; Starick, E; Harder, T; Weissenböck, H; Lamp, B; Hammer, SE; Ladinig, A; Saalmüller, A; Gerner, W

Title: Influenza A Virus Infection in Pigs Attracts Multifunctional and Cross-Reactive T Cells to the Lung.

Source: J Virol. 2016; 90(20):9364-9382

Authors Vetmeduni Vienna:

Gerner Wilhelm
Graage Robert
Hammer Sabina
Koinig Hanna
Ladinig Andrea
Lamp Benjamin
Mair Kerstin
Rodriguez Gomez Irene Magdalena
Saalmüller Armin
Stadler Maria
Talker Stephanie
Weissenböck Herbert

Vetmed Research Units
Institute of Immunology
Institute of Pathology
Institute of Virology
University Clinic for Swine

Pigs are natural hosts for influenza A viruses and play a critical role in influenza epidemiology. However, little is known about their influenza-evoked T-cell response. We performed a thorough analysis of both the local and systemic T-cell response in influenza virus-infected pigs, addressing kinetics and phenotype as well as multifunctionality (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]) and cross-reactivity. A total of 31 pigs were intratracheally infected with an H1N2 swine influenza A virus (FLUAVsw) and consecutively euthanized. Lungs, tracheobronchial lymph nodes, and blood were sampled during the first 15 days postinfection (p.i.) and at 6 weeks p.i. Ex vivo flow cytometry of lung lymphocytes revealed an increase in proliferating (Ki-67(+)) CD8(+) T cells with an early effector phenotype (perforin(+) CD27(+)) at day 6 p.i. Low frequencies of influenza virus-specific IFN-γ-producing CD4(+) and CD8(+) T cells could be detected in the lung as early as 4 days p.i. On consecutive days, influenza virus-specific CD4(+) and CD8(+) T cells produced mainly IFN-γ and/or TNF-α, reaching peak frequencies around day 9 p.i., which were up to 30-fold higher in the lung than in tracheobronchial lymph nodes or blood. At 6 weeks p.i., CD4(+) and CD8(+) memory T cells had accumulated in lung tissue. These cells showed diverse cytokine profiles and in vitro reactivity against heterologous influenza virus strains, all of which supports their potential to combat heterologous influenza virus infections in pigs.Pigs not only are a suitable large-animal model for human influenza virus infection and vaccine development but also play a central role in the emergence of new pandemic strains. Although promising candidate universal vaccines are tested in pigs and local T cells are the major correlate of heterologous control, detailed and targeted analyses of T-cell responses at the site of infection are scarce. With the present study, we provide the first detailed characterization of magnitude, kinetics, and phenotype of specific T cells recruited to the lungs of influenza virus-infected pigs, and we could demonstrate multifunctionality, cross-reactivity, and memory formation of these cells. This, and ensuing work in the pig, will strengthen the position of this species as a large-animal model for human influenza virus infection and will immediately benefit vaccine development for improved control of influenza virus infections in pigs.Copyright © 2016 Talker et al.

Keywords Pubmed: Animals
CD4-Positive T-Lymphocytesimmunologyvirology
CD8-Positive T-Lymphocytesimmunology
Cross Reactionsimmunology
Influenza A Virus, H1N2 Subtypeimmunology
Influenza Vaccinesimmunology
Orthomyxoviridae Infectionsimmunology
Swine Diseasesimmunologyvirology
Tumor Necrosis Factor-alphaimmunology

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