Interleukin-15 mediates protection against experimental tuberculosis: A role for NKG2D-dependent effector mechanisms of CD8+ T cells

Alexandra Rausch, Manuela Heßmann, Alexandra Hölscher, Tanja Schreiber, Silvia Bulfone-Paus, Stefan Ehlers, Christoph Hölscher

    Research output: Contribution to journalArticlepeer-review

    Abstract

    CD8+ T cells are involved in protection against Mycobacterium tuberculosis infection and represent a promising target for new vaccine strategies. Because IL-15 is important for the homeostasis of CD8+ T cells, we studied the immune response in IL-15-deficient mice during tuberculosis. In the absence of IL-15, CD8+ T cells failed to efficiently accumulate in draining lymph nodes and at the site of infection. The expression of antigen-specific effector functions, such as the production of interferon-γ and cytotoxicity, were impaired in CD8+ T cells, but not CD4+ T cells, from IL-15-deficient mice. This defect was associated with an increased mortality of IL-15-deficient mice during the chronic phase of infection. The lectin-like stimulatory receptor natural killer group 2D (NKG2D) was up-regulated on CD8+ T cells only from wild-type mice, but not from IL-15-deficient mice. Mechanistically, blocking NKG2D function with an mAb inhibited M. tuberculosis-directed CD8+ T cell responses in vitro. We conclude that in addition to regulating the expansion of CD8+ T cells, IL-15 is also necessary for inducing effector mechanisms in CD8+ T cells that depend on NKG2D expression. Hence, our results implicate IL-15 and NKG2D as promising targets for modulating CD8+ T cell-mediated protection against tuberculosis. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Original languageEnglish
    Pages (from-to)1156-1167
    Number of pages11
    JournalEuropean journal of immunology
    Volume36
    Issue number5
    DOIs
    Publication statusPublished - May 2006

    Keywords

    • Bacterial infection
    • Cytokine receptor
    • Cytokines
    • Rodent
    • T cells

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