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

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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Figure 1

Viral infection induces the expression of cell-cycle genes by memory CD8+ T cells.

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Viral infection induces the expression of cell-cycle genes by memory CD8...
(A) Number of genes differentially expressed in memory P14 cells on day 4 following PV infection compared with mock infection. (B) Heat map of differentially expressed genes. Each vertical lane represents an independent RNA pool. Color scale represents relative intensity of expression for each individual gene. (C) Expression levels of the 67 genes identified as belonging to the cell-cycle GO term by DAVID analysis in memory P14 cells exposed to virus-driven inflammation compared with saline-treated groups. Arrow indicates gene that encodes the Ki-67 protein. Data are from 3 independent RNA pools per group collected from at least 2 mice per pool (1 × 106 purified memory P14 cells per pool).