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

Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):16472-7. doi: 10.1073/pnas.1407393111. Epub 2014 Sep 29.

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

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity / immunology*
  • Adjuvants, Immunologic
  • Adoptive Transfer
  • Animals
  • Bacterial Vaccines / immunology*
  • CD40 Antigens / immunology
  • Female
  • Immunologic Memory
  • Interleukins / physiology*
  • Listeriosis / immunology
  • Listeriosis / prevention & control
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Ovalbumin / immunology
  • Poly I-C / immunology
  • Radiation Chimera
  • Receptors, Cytokine / deficiency
  • Receptors, Cytokine / physiology
  • Receptors, Interleukin
  • STAT Transcription Factors / deficiency
  • STAT Transcription Factors / physiology
  • Smallpox Vaccine / immunology
  • T-Cell Antigen Receptor Specificity
  • T-Lymphocyte Subsets / immunology*
  • Toll-Like Receptors / immunology
  • Transcription, Genetic / immunology
  • Vaccination*
  • Vaccines, Subunit / immunology
  • Vaccinia / immunology
  • Vaccinia / prevention & control

Substances

  • Adjuvants, Immunologic
  • Bacterial Vaccines
  • CD40 Antigens
  • Il27 protein, mouse
  • Il27ra protein, mouse
  • Interleukins
  • Receptors, Cytokine
  • Receptors, Interleukin
  • STAT Transcription Factors
  • Smallpox Vaccine
  • Toll-Like Receptors
  • Vaccines, Subunit
  • Ovalbumin
  • Poly I-C