Influenza A virus infection in pigs attracts multifunctional and cross-reactive T cells to the lung
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+) CD8+ T cells with an early effector phenotype (perforin+CD27+) at day 6 pi. Low frequencies of influenza-specific IFN-γ producing CD4+ and CD8+ T cells could be detected in the lung as early as 4 days pi. On consecutive days, influenza-specific CD4+ and CD8+ 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+ and CD8+ 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.