New Insights into the Generation of CD4 Memory May Shape Future Vaccine Strategies for Influenza
Authors
Devarajan, PriyadharshiniBautista, Bianca L.
Vong, Allen M.
McKinstry, K. Kai
Strutt, Tara M.
Swain, Susan L.
UMass Chan Affiliations
Graduate School of Biomedical Sciences, Program in Immunology and MicrobiologyDepartment of Pathology
Document Type
Journal ArticlePublication Date
2016-04-11Keywords
CD4 T cellscell-mediated immunity
influenza
late-antigen
memory checkpoint
vaccination
Immunology of Infectious Disease
Immunopathology
Immunoprophylaxis and Therapy
Influenza Virus Vaccines
Virology
Virus Diseases
Metadata
Show full item recordAbstract
Influenza viral evolution presents a formidable challenge to vaccination due to the virus' ability to rapidly mutate to evade immune responses. Live influenza infections generate large and diverse CD4 effector T cell responses that yield highly protective, long-lasting CD4 T cell memory that can target conserved viral epitopes. We review advances in our understanding of mechanisms involved in generating CD4 T cell responses against the influenza A virus (IAV), focusing on specialized follicular helper (TFH) and CD4 cytotoxic (ThCTL) effector subsets and on CD4 T cell memory. We also discuss two recent findings in context of enhancing vaccine responses. First, helper T cells require priming with APC secreting high levels of IL-6. Second, the transition of IAV-generated effectors to memory depends on IL-2, costimulation and antigen signals, just before effectors reach peak numbers, defined as the "memory checkpoint." The need for these signals during the checkpoint could explain why many current influenza vaccines are poorly effective and elicit poor cellular immunity. We suggest that CD4 memory generation can be enhanced by re-vaccinating at this time. Our best hope lies in a universal vaccine that will not need to be formulated yearly against seasonal antigenically novel influenza strains and will also be protective against a pandemic strain. We suggest a vaccine approach that elicits a powerful T cell response, by initially inducing high levels of APC activation and later providing antigen at the memory checkpoint, may take us a step closer to such a universal influenza vaccine.Source
Front Immunol. 2016 Apr 11;7:136. doi: 10.3389/fimmu.2016.00136. eCollection 2016. Link to article on publisher's siteDOI
10.3389/fimmu.2016.00136Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40096PubMed ID
27148257Related Resources
Link to Article in PubMedDistribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.3389/fimmu.2016.00136
Scopus Count
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/