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

Due to their ability to rapidly proliferate and produce effector cytolcines, 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 CDEVT 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.