Trends in Immunology
ReviewT cell responses during influenza infection: getting and keeping control
Section snippets
The continuing threat of influenza infection
In 1918–1919, an outbreak of severe respiratory infection, the so-called ‘Spanish flu’, occurred, which rapidly spread through the human population and resulted in an estimated 20–50 million deaths worldwide. The agent that caused this catastrophe was subsequently revealed to be a type A influenza virus (IAV) strain. Unique features of IAV structure, replication, transmissibility among certain species, and the existence of zoonotic reservoirs make this viral pathogen ideally suited to escape
Control of T cell activation and differentiation by respiratory dendritic cells
The outcome of viral infections is determined by a series of intricate interactions between the pathogen and host. At mucosal surfaces like the respiratory tract (RT), epithelial cells that line the RT are not only the primary cell types that support the productive replication of IAV, but they also serve as the first line of host defense against infection (reviewed in 4, 5). The respiratory epithelial layer is a heterogeneous array of CD45– cells, including ciliated and non-ciliated airway
T cell responses within influenza-infected lungs
Along with their roles as initiators and regulators of innate and adaptive immune responses to influenza, respiratory epithelial cells are the primary target of the immune response because they are the major cell types that are capable of supporting productive infection (release of fully infectious virions) by most influenza virus strains 4, 6. Thus, infected respiratory epithelial cells not only regulate the immune response, but also represent an essential target of immune recognition whose
The Ying and Yang of injury control by effector T cell immune responses in the infected lung
Along with the ability to clear IAV infection, antiviral T cells can be a significant contributor to pulmonary inflammation and injury. The mechanisms of T cell-induced injury might be both direct and indirect. Antiviral CD8+ and CD4+ T cells are able to lyse antigen-bearing lung epithelial cells directly, and can contribute to airway exudates during the process of viral clearance. Antiviral T cells are also the major sources of proinflammatory cytokines/chemokines (e.g. IFN-γ, TNF-α, IL-17,
Concluding remarks
Over the past several years, we have gained new insight into the induction of antiviral T cell responses in the DLNs, and the expression of effector and regulatory activity by these T cells in the infected lungs during IAV infection. The identification of crucial roles for migrant RDCs in the priming of IAV-specific T cells, and for inflammatory DCs in further maintaining and controlling local T cell responses in the lung, have established DCs as central regulators of the magnitude and quality
Acknowledgments
We thank members of the Braciale Laboratory for helpful discussions, and colleagues who provided recent publications. As a result of space limitations, we apologize for being unable to cite many primary references relevant to the topic of this review. This study was supported by grants from the National Institutes of Health (RO1 AI-15608, RO1 AI-37293, RO1 HL-33391, and U-19 AI-83024) to T.J. Braciale.
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These authors contributed equally to this work.