Abstract
Our new molecular understanding of immune priming states that dendritic cell (DC) activation is absolutely pivotal for expansion and differentiation of naïve T lymphocytes, and it follows that understanding DC activation is essential to understand and design vaccine adjuvants. This chapter describes how dendritic cells can be used as a core tool to provide detailed quantitative and predictive immunomics information about how adjuvants function. The role of distinct antigen, costimulation, and differentiation signals from activated DC in priming is explained. Four categories of input signals which control DC activation—direct pathogen detection, sensing of injury or cell death, indirect activation via endogenous proinflammatory mediators, and feedback from activated T cells—are compared and contrasted. Practical methods for studying adjuvants using DC are summarized and the importance of DC subset choice, simulating T cell feedback, and use of knockout cells is highlighted. Finally, five case studies are examined that illustrate the benefit of DC activation analysis for understanding vaccine adjuvant function.
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Disclaimer
The effectiveness of your adjuvant can go down as well as up. The complexity of both the innate and adaptive immune systems should never be underestimated. In this chapter, one antigen presenting cell, three T cell priming signals, and four input signals are discussed. Although DCs take a central role in controlling immune priming and polarization, other cell types have an equally important role in both sensing antigen and controlling immunity. Similarly, classification of DC–T cell signals into three categories is helpful; however, in reality, the interaction between these cells is so complex that it is termed the immune synapse, and many signals fall into more than one category. Although signal 3 is conceptually vital, and study of cytokines in this class such as IL-12 has proven highly informative, much is still unknown about what signals lead to which immune responses. Worse, for many important pathogens, the class of immunity required for protection is still unclear. DC studies are only a simple starting point and all adjuvants must ultimately be tested in vivo to determine efficacy.
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Edwards, A.D. (2013). What Have Dendritic Cells Ever Done for Adjuvant Design? Cellular and Molecular Methods for the Rational Development of Vaccine Adjuvants. In: Flower, D., Perrie, Y. (eds) Immunomic Discovery of Adjuvants and Candidate Subunit Vaccines. Immunomics Reviews:, vol 5. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5070-2_8
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DOI: https://doi.org/10.1007/978-1-4614-5070-2_8
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