First Author | Pennock ND | Year | 2014 |
Journal | Proc Natl Acad Sci U S A | Volume | 111 |
Issue | 46 | Pages | 16472-7 |
PubMed ID | 25267651 | Mgi Jnum | J:216441 |
Mgi Id | MGI:5608817 | Doi | 10.1073/pnas.1407393111 |
Citation | Pennock ND, et al. (2014) 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 111(46):16472-7 |
abstractText | 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-27Ralpha. 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. |