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

Author:
Pennock, Nathan D., Gapin, Laurent, Kedl, Ross M.
Source:
Proceedings of the National Academy of Sciences of the United States of America 2014 v.111 no.46 pp. 16472-16477
ISSN:
0027-8424
Subject:
T-lymphocytes, adjuvants, bacteria, cytokines, immune response, immunization, neoplasms, neutralizing antibodies, pathogens, proteins, subunit vaccines, viruses
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.
Agid:
1787817