Influenza virus-specific CD4+ and CD8+ T cell-mediated immunity induced by infection and vaccination

•CD4+ and CD8+ T cells are important correlates of protection.•CD4+ T cells provide help to B cells and support CD8+ T cell expansion.•CD8+ T cell responses are highly cross-reactive and contribute to heterosubtypic protection.•TRM mediate protection at the site of influenza virus entry. Influenza A and B virus infections are a major cause of respiratory disease in humans and are responsible for substantial morbidity and mortality worldwide. Vaccination against influenza mainly aims at the induction of virus neutralizing serum antibodies, which are an important correlate of protection provided that the antibodies match the strains causing the outbreaks antigenically. In addition, virus-specific T cells are known to contribute to protective immunity to influenza virus infections by limiting duration and severity of the disease. As the majority of virus-specific T cells recognize epitopes located in relatively conserved proteins, like the Nucleoprotein and Matrix 1 protein, they display a high degree of cross-reactivity with a wide range of influenza viruses, including newly emerging viruses of alternative subtypes. Advancing our understanding of influenza virus-specific T cell responses and their role in protective immunity against influenza will aid the rational design of novel vaccines that could induce robust, broad and long-lasting immune responses. Here, we discuss the contribution of influenza virus-specific CD4+ and CD8+ T cells to protective immunity against influenza infection and the requirements and strategies for their induction by natural infection or vaccination, especially in children.