tetano
Editor, Senior Moderator
J Virol. 2016 Aug 10. pii: JVI.01211-16. [Epub ahead of print]
[h=1]Influenza A virus infection in pigs attracts multifunctional and cross-reactive T cells to the lung.[/h] Talker SC[SUP]1[/SUP], Stadler M[SUP]1[/SUP], Koinig HC[SUP]2[/SUP], Mair KH[SUP]1[/SUP], Rodr?guez-G?mez IM[SUP]1[/SUP], Graage R[SUP]2[/SUP], Zell R[SUP]3[/SUP], D?rrwald R[SUP]4[/SUP], Starick E[SUP]5[/SUP], Harder T[SUP]5[/SUP], Weissenb?ck H[SUP]6[/SUP], Lamp B[SUP]7[/SUP], Hammer SE[SUP]1[/SUP], Ladinig A[SUP]2[/SUP], Saalm?ller A[SUP]1[/SUP], Gerner W[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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-infected pigs, addressing kinetics and phenotype, as well as multifunctionality (IFN-γ, TNF-α, IL-2) and cross-reactivity. A total of 31 pigs were intratracheally infected with an H1N2 swine influenza A virus (FLUAVsw) and consecutively euthanized. Lung, tracheobronchial lymph nodes and blood were sampled during the first 15 days post infection (pi) and at six weeks pi. Ex vivo flow cytometry of lung lymphocytes revealed an increase in proliferating (Ki-67[SUP]+[/SUP]) CD8[SUP]+[/SUP] T cells with an early effector phenotype (perforin[SUP]+[/SUP]CD27[SUP]+[/SUP]) at day 6 pi. Low frequencies of influenza-specific IFN-γ producing CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells could be detected in the lung as early as 4 days pi. On consecutive days, influenza-specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells produced mainly IFN-γ and/or TNF-α, reaching peak frequencies around day 9 pi, which were up to 30-fold higher in the lung compared with tracheobronchial lymph nodes or blood. Six weeks pi, CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] memory T cells had accumulated in lung tissue. These cells showed diverse cytokine profiles and in vitro reactivity against heterologous influenza strains, all of which supports their potential to combat heterologous influenza infections in pigs.
[h=4]IMPORTANCE:[/h] Pigs are not only a suitable large-animal model for human influenza 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-infected pigs, and 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 infection and will immediately benefit vaccine development for improved control of influenza infections in pigs.
Copyright ? 2016 Talker et al.
PMID: 27512056 DOI: 10.1128/JVI.01211-16
[PubMed - as supplied by publisher]
[h=1]Influenza A virus infection in pigs attracts multifunctional and cross-reactive T cells to the lung.[/h] Talker SC[SUP]1[/SUP], Stadler M[SUP]1[/SUP], Koinig HC[SUP]2[/SUP], Mair KH[SUP]1[/SUP], Rodr?guez-G?mez IM[SUP]1[/SUP], Graage R[SUP]2[/SUP], Zell R[SUP]3[/SUP], D?rrwald R[SUP]4[/SUP], Starick E[SUP]5[/SUP], Harder T[SUP]5[/SUP], Weissenb?ck H[SUP]6[/SUP], Lamp B[SUP]7[/SUP], Hammer SE[SUP]1[/SUP], Ladinig A[SUP]2[/SUP], Saalm?ller A[SUP]1[/SUP], Gerner W[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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-infected pigs, addressing kinetics and phenotype, as well as multifunctionality (IFN-γ, TNF-α, IL-2) and cross-reactivity. A total of 31 pigs were intratracheally infected with an H1N2 swine influenza A virus (FLUAVsw) and consecutively euthanized. Lung, tracheobronchial lymph nodes and blood were sampled during the first 15 days post infection (pi) and at six weeks pi. Ex vivo flow cytometry of lung lymphocytes revealed an increase in proliferating (Ki-67[SUP]+[/SUP]) CD8[SUP]+[/SUP] T cells with an early effector phenotype (perforin[SUP]+[/SUP]CD27[SUP]+[/SUP]) at day 6 pi. Low frequencies of influenza-specific IFN-γ producing CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells could be detected in the lung as early as 4 days pi. On consecutive days, influenza-specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells produced mainly IFN-γ and/or TNF-α, reaching peak frequencies around day 9 pi, which were up to 30-fold higher in the lung compared with tracheobronchial lymph nodes or blood. Six weeks pi, CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] memory T cells had accumulated in lung tissue. These cells showed diverse cytokine profiles and in vitro reactivity against heterologous influenza strains, all of which supports their potential to combat heterologous influenza infections in pigs.
[h=4]IMPORTANCE:[/h] Pigs are not only a suitable large-animal model for human influenza 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-infected pigs, and 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 infection and will immediately benefit vaccine development for improved control of influenza infections in pigs.
Copyright ? 2016 Talker et al.
PMID: 27512056 DOI: 10.1128/JVI.01211-16
[PubMed - as supplied by publisher]