title: 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.forename: Martin J
authors.initials: MJ
authors.lastname: Richer
authors.forename: Lecia L
authors.initials: LL
authors.lastname: Pewe
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Hancox
authors.forename: Stacey M
authors.initials: SM
authors.lastname: Hartwig
authors.forename: Steven M
authors.initials: SM
authors.lastname: Varga
authors.forename: John T
authors.initials: JT
authors.lastname: Harty
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002455:Cell Division / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000235:genetics / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology
chemical_list: C569274:IL15 protein, human; D007370:Interferon Type I; D019409:Interleukin-15; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases