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- Title
Inflammatory IL-15 is required for optimal memory T cell responses.
- Authors
Richer, Martin J.; Pewe, Lecia L.; Hancox, Lisa S.; Hartwig, Stacey M.; Varga, Steven M.; Harty, John T.
- Abstract
Due to their ability to rapidly proliferate and produce effector cytokines, memory CD8+ T cells increase protection following reexposure to a pathogen. However, low inflammatory immunizations do not provide memory CD8+ T cells with a proliferation advantage over naive CD8+ T cells, suggesting that cell-extrinsic factors enhance memory CD8+ T cell proliferation in vivo. Herein, we demonstrate that inflammatory signals are critical for the rapid proliferation of memory CD8+ T cells following infection. Using murine models of viral infection and antigen exposure, we found that type I IFN-driven expression of IL-15 in response to viral infection prepares memory CD8+ T cells for rapid division independently of antigen reexposure by transiently inducing cell-cycle progression via a pathway dependent on mTOR complex-1 (mTORC1). Moreover, exposure to IL-15 allowed more rapid division of memory CD8+ T cells following antigen encounter and enhanced their protective capacity against viral infection. Together, these data reveal that inflammatory IL-15 promotes optimal responses by memory CD8+ T cells.
- Subjects
T cells; PHYSIOLOGICAL effects of cytokines; PATHOGENIC microorganisms; VIRUS diseases; ANTIGENS
- Publication
Journal of Clinical Investigation, 2015, Vol 125, Issue 9, p3477
- ISSN
0021-9738
- Publication type
Article
- DOI
10.1172/JCI81261