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Inflammatory IL-15 is required for optimal memory T cell responses
Martin J. Richer, … , Steven M. Varga, John T. Harty
Martin J. Richer, … , Steven M. Varga, John T. Harty
Published August 4, 2015
Citation Information: J Clin Invest. 2015;125(9):3477-3490. https://doi.org/10.1172/JCI81261.
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Research Article Immunology

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

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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.

Authors

Martin J. Richer, Lecia L. Pewe, Lisa S. Hancox, Stacey M. Hartwig, Steven M. Varga, John T. Harty

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