Abstract
Although much is known about the mechanisms by which pathogen recognition drives the initiation of T cell responses, including those to respiratory viruses, the role of pathogen recognition in fate decisions of T cells once they have become effectors remains poorly defined. Here, we review our recent studies that suggest that the generation of CD4 T cell memory is determined by recognition of virus at an effector “checkpoint.” We propose this is also true of more highly differentiated tissue-restricted effector cells, including cytotoxic “ThCTL” in the site of infection and TFH in secondary lymphoid organs. We point out that ThCTL are key contributors to direct viral clearance and TFH to effective Ab response, suggesting that the most protective immunity to influenza, and by analogy to other respiratory viruses, requires prolonged exposure to antigen and to infection-associated signals. We point out that many vaccines used today do not provide such prolonged signals and suggest this contributes to their limited effectiveness. We also discuss how aging impacts effective CD4 T cell responses and how new insights about the response of aged naive CD4 T cells and B cells might hold implications for effective vaccine design for both the young and aged against respiratory viruses.
Highlights
Host defense to influenza infection begins when lung airway epithelial cells, dendritic cells (DC), and alveolar macrophages alert the host to the presence of virus through the activation of pattern recognition receptors (PRR) [1]
We found that antigen presentation throughout the effector response was required for almost all CD4 T cell memory generated by Influenza A virus (IAV) infection [7, 8]
Effector CD4 T cells infiltrate the tissues throughout the body [24], that kill infected cells (ThCTL) are only found in the lung and we find that they upregulate a gene expression program consistent with tissue residency [20]
Summary
Swain SL (2018) Pathogen Recognition by CD4 Effectors Drives Key Effector and Most Memory Cell Generation Against Respiratory Virus. We point out that ThCTL are key contributors to direct viral clearance and TFH to effective Ab response, suggesting that the most protective immunity to influenza, and by analogy to other respiratory viruses, requires prolonged exposure to antigen and to infection-associated signals. Host defense to influenza infection begins when lung airway epithelial cells, dendritic cells (DC), and alveolar macrophages alert the host to the presence of virus through the activation of pattern recognition receptors (PRR) [1]. This triggers the production of inflammatory cytokines, which activates antigen-presenting cells (APC). When virus surface proteins hemaggluttinin (HA) and neuraminidase (NA) can mutate sufficiently and escape
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
