期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2014
卷号：111
期号：46
页码：16472-16477
DOI：10.1073/pnas.1407393111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceTraditional immunizations involve the controlled introduction of attenuated bacteria or viruses, allowing for generation of immunity prior to exposure to the dangerous native pathogen. In contrast, subunit immunization utilizes only pieces of the pathogen combined with a separate immune stimulatory agent (adjuvant). Although subunit immunizations do generate effective neutralizing antibodies, they do not generate robust T-cell responses. T cells provide therapeutic benefit by directly inducing cell lysis and shaping the immune response through soluble proteins (cytokines) critical for intervening in cancer and viral infection. Here, we demonstrate that subunit vaccines are uniquely and unexpectedly dependent on the cytokine IL-27 for making strong T-cell responses. 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-27R. 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.
