Inflammatory IL-15 is required for optimal memory T cell responses

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 c...

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Bibliographic Details
Published in:The Journal of clinical investigation 2015-09, Vol.125 (9), p.3477-3490
Main Authors: Richer, Martin J, Pewe, Lecia L, Hancox, Lisa S, Hartwig, Stacey M, Varga, Steven M, Harty, John T
Format: Article
Language:English
Subjects:
Animals
Biomedical research
Blood & organ donations
CD8 lymphocytes
CD8-Positive T-Lymphocytes - cytology
CD8-Positive T-Lymphocytes - immunology
Cell cycle
Cell Division - genetics
Cell Division - immunology
Cloning
Colleges & universities
Cytokines
Flow cytometry
Genetic aspects
Health aspects
Humans
Immunoglobulins
Immunologic Memory
Infections
Inflammation
Interferon Type I - genetics
Interferon Type I - immunology
Interleukin-15
Interleukin-15 - genetics
Interleukin-15 - immunology
Kinases
Lymphocytes
Mechanistic Target of Rapamycin Complex 1
Mice
Mice, Knockout
Multiprotein Complexes - genetics
Multiprotein Complexes - immunology
Physiological aspects
Scholarships & fellowships
T cell receptors
TOR Serine-Threonine Kinases - genetics
TOR Serine-Threonine Kinases - immunology
Viral infections
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Summary: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.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI81261