CD4 T cells in protection from influenza virus: Viral antigen specificity and functional potential

• Published in: Immunological reviews 2018-07, Vol.284 (1), p.91-105
• Main Authors: Sant, Andrea J., DiPiazza, Anthony T., Nayak, Jennifer L., Rattan, Ajitanuj, Richards, Katherine A.
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Animal models; Animals; Antibodies, Viral - immunology; antigen; Antigens; Antigens, Viral - immunology; B-Lymphocytes; CD4 antigen; CD4 T cells; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; Discrete functions; Disease Models, Animal; Epitopes; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Human behavior; human immunity; Humans; Immunity; immunodominance; Immunologic Memory - immunology; Immunological memory; Infections; Influenza; Influenza A; Influenza A Virus, H1N1 Subtype - immunology; Influenza, Human - immunology; lung; Lungs; Lymphocytes; Lymphocytes B; Lymphocytes T; Memory cells; Mice; Pandemics; Strains (organisms); vaccine responses; Vaccines; Viruses
• ISSN: 0105-2896; 1600-065X
• DOI: 10.1111/imr.12662

Summary CD4 T cells convey a number of discrete functions to protective immunity to influenza, a complexity that distinguishes this arm of adaptive immunity from B cells and CD8 T cells. Although the most well recognized function of CD4 T cells is provision of help for antibody production, CD4 T cells are important in many aspects of protective immunity. Our studies have revealed that viral antigen specificity is a key determinant of CD4 T cell function, as illustrated both by mouse models of infection and human vaccine responses, a factor whose importance is due at least in part to events in viral antigen handling. We discuss research that has provided insight into the diverse viral epitope specificity of CD4 T cells elicited after infection, how this primary response is modified as CD4 T cells home to the lung, establish memory, and after challenge with a secondary and distinct influenza virus strain. Our studies in human subjects point out the challenges facing vaccine efforts to facilitate responses to novel and avian strains of influenza, as well as strategies that enhance the ability of CD4 T cells to promote protective antibody responses to both seasonal and potentially pandemic strains of influenza.