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

Eur J Immunol. 2006 May;36(5):1156-67. doi: 10.1002/eji.200535290.


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-gamma 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Interferon-gamma / biosynthesis
  • Interleukin-15 / physiology*
  • Mice
  • Mice, Inbred C57BL
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic / physiology*
  • Receptors, Natural Killer Cell
  • Tuberculosis / immunology*


  • Interleukin-15
  • Klrk1 protein, mouse
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Interferon-gamma