Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adaptive Immunity / immunology*
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Adjuvants, Immunologic
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Adoptive Transfer
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Animals
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Bacterial Vaccines / immunology*
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CD40 Antigens / immunology
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Female
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Immunologic Memory
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Interleukins / physiology*
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Listeriosis / immunology
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Listeriosis / prevention & control
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Lymphocyte Activation
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Ovalbumin / immunology
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Poly I-C / immunology
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Radiation Chimera
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Receptors, Cytokine / deficiency
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Receptors, Cytokine / physiology
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Receptors, Interleukin
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STAT Transcription Factors / deficiency
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STAT Transcription Factors / physiology
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Smallpox Vaccine / immunology
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T-Cell Antigen Receptor Specificity
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T-Lymphocyte Subsets / immunology*
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Toll-Like Receptors / immunology
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Transcription, Genetic / immunology
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Vaccination*
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Vaccines, Subunit / immunology
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Vaccinia / immunology
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Vaccinia / prevention & control
Substances
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Adjuvants, Immunologic
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Bacterial Vaccines
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CD40 Antigens
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Il27 protein, mouse
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Il27ra protein, mouse
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Interleukins
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Receptors, Cytokine
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Receptors, Interleukin
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STAT Transcription Factors
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Smallpox Vaccine
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Toll-Like Receptors
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Vaccines, Subunit
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Ovalbumin
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Poly I-C