title: IL-27 is required for shaping the magnitude, affinity distribution, and memory of T cells responding to subunit immunization.
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.
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Denver, Aurora, CO 80045.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Pennock
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Denver, Aurora, CO 80045.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gapin
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Denver, Aurora, CO 80045 ross.kedl@ucdenver.edu.
authors.forename: Ross M
authors.initials: RM
authors.lastname: Kedl
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000276:Adjuvants, Immunologic; D019264:Adoptive Transfer; D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D005260:Female; D007156:Immunologic Memory; D007378:Interleukins / Q000502:physiology*; D008088:Listeriosis / Q000276:immunology / Q000517:prevention & control; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011070:Poly I-C / Q000276:immunology; D011828:Radiation Chimera; D018121:Receptors, Cytokine / Q000172:deficiency / Q000502:physiology; D018123:Receptors, Interleukin; D050791:STAT Transcription Factors / Q000172:deficiency / Q000502:physiology; D012900:Smallpox Vaccine / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology; D014611:Vaccination; D022223:Vaccines, Subunit / Q000276:immunology; D014615:Vaccinia / Q000276:immunology / Q000517:prevention & control
chemical_list: D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; D019013:CD40 Antigens; C486767:Il27 protein, mouse; C484747:Il27ra protein, mouse; D007378:Interleukins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D050791:STAT Transcription Factors; D012900:Smallpox Vaccine; D051193:Toll-Like Receptors; D022223:Vaccines, Subunit; D010047:Ovalbumin; D011070:Poly I-C