Chapter

Influenza Pathogenesis and Control - Volume II

Volume 386 of the series Current Topics in Microbiology and Immunology pp 399-421

Date:

Memory CD4 T Cells in Influenza

  • Kyra D. ZensAffiliated withColumbia Center for Translational Immunology, Columbia University Medical CenterDepartment of Microbiology and Immunology, Columbia University Medical Center
  • , Donna L. FarberAffiliated withColumbia Center for Translational Immunology, Columbia University Medical CenterDepartment of Microbiology and Immunology, Columbia University Medical CenterDepartment of Surgery, Columbia University Medical Center Email author 

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Abstract

Influenza A virus is a significant cause of morbidity and mortality worldwide, particularly among young children and the elderly. Current vaccines induce neutralizing antibody responses directed toward highly variable viral surface proteins, resulting in limited heterosubtypic protection to new viral serotypes. By contrast, memory CD4 T cells recognize conserved viral proteins and are cross-reactive to multiple influenza strains. In humans, virus-specific memory CD4 T cells were found to be the protective correlate in human influenza challenge studies, suggesting their key role in protective immunity. In mouse models, memory CD4 T cells can mediate protective responses to secondary influenza infection independent of B cells or CD8 T cells, and can influence innate immune responses. Importantly, a newly defined, tissue-resident CD4 memory population has been demonstrated to be retained in lung tissue and promote optimal protective responses to an influenza infection. Here, we review the current state of results regarding the generation of memory CD4 T cells following primary influenza infection, mechanisms for their enhanced efficacy in protection from secondary challenge including their phenotype, localization, and function in the context of both mouse models and human infection. We also discuss the generation of memory CD4 T cells in response to influenza vaccines and its future implications for vaccinology.