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

J Clin Invest. 2015 Sep;125(9):3477-90. doi: 10.1172/JCI81261. Epub 2015 Aug 4.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Division / genetics
  • Cell Division / immunology*
  • Humans
  • Immunologic Memory*
  • Interferon Type I / genetics
  • Interferon Type I / immunology
  • Interleukin-15 / genetics
  • Interleukin-15 / immunology*
  • Mechanistic Target of Rapamycin Complex 1
  • Mice
  • Mice, Knockout
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / immunology
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / immunology

Substances

  • IL15 protein, human
  • Interferon Type I
  • Interleukin-15
  • Multiprotein Complexes
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1