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IL-27 is required for shaping the magnitude, affinity distribution, and memory of T cells responding to subunit immunization

Pennock, Nathan D., Gapin, Laurent, Kedl, Ross M.
Proceedings of the National Academy of Sciences of the United States of America 2014 v.111 no.46 pp. 16472-16477
T-lymphocytes, adjuvants, bacteria, cytokines, immune response, immunization, neoplasms, neutralizing antibodies, pathogens, proteins, subunit vaccines, viruses
An elusive goal of cellular immune vaccines is the generation of large numbers of antigen-specific T cells in response to subunit immunization. A broad spectrum of cytokines and cell-surface costimulatory molecules are known to shape the programming, magnitude, and repertoire of T cells responding to vaccination. We show here that the majority of innate immune receptor agonist-based vaccine adjuvants unexpectedly depend on IL-27 for eliciting CD4 ⁺ and CD8 ⁺ T-cell responses. This is in sharp contrast to infectious challenge, which generates T-cell responses that are IL-27–independent. Mixed bone marrow chimera experiments demonstrate that IL-27 dependency is T cell-intrinsic, requiring T-cell expression of IL-27Rα. Further, we show that IL-27 dependency not only dictates the magnitude of vaccine-elicited T-cell responses but also is critical for the programming and persistence of high-affinity T cells to subunit immunization. Collectively, our data highlight the unexpected central importance of IL-27 in the generation of robust, high-affinity cellular immune responses to subunit immunization.