Loss of NKG2D in murine NK cells leads to increased perforin production upon long-term stimulation with IL-2

Daniela Prinz, Klara Klein, Julia List, Vanessa M Knab, Ingeborg Menzl, Nicoletta Leidenfrost, Gerwin Heller, Bojan Polić, Eva Maria Putz, Agnieszka Witalisz-Siepracka, Veronika Sexl, Dagmar Gotthardt

Research output: Journal article (peer-reviewed)Journal article

9 Citations (Scopus)


NK cells are innate lymphocytes responsible for lysis of pathogen-infected and transformed cells. One of the major activating receptors required for target cell recognition is the NK group 2D (NKG2D) receptor. Numerous reports show the necessity of NKG2D for effective tumor immune surveillance. Further studies identified NKG2D as a key element allowing tumor immune escape. We here use a mouse model with restricted deletion of NKG2D in mature NKp46+ cells (NKG2DΔNK ). NKG2DΔNK NK cells develop normally, have an unaltered IFN-γ production but kill tumor cell lines expressing NKG2D ligands (NKG2DLs) less efficiently. However, upon long-term stimulation with IL-2, NKG2D-deficient NK cells show increased levels of the lytic molecule perforin. Thus, our findings demonstrate a dual function of NKG2D for NK cell cytotoxicity; while NKG2D is a crucial trigger for cytotoxicity of tumor cells expressing activating ligands it is also capable to limit perforin production in IL-2 activated NK cells.

Original languageEnglish
Pages (from-to)880-890
Number of pages11
JournalEuropean Journal of Immunology
Issue number6
Publication statusPublished - Jun 2020
Externally publishedYes


  • Animals
  • Cell Line, Tumor
  • Immunity, Cellular/drug effects
  • Interferon-gamma/genetics
  • Interleukin-2/pharmacology
  • Killer Cells, Natural/immunology
  • Mice
  • Mice, Knockout
  • NK Cell Lectin-Like Receptor Subfamily K/genetics
  • Pore Forming Cytotoxic Proteins/genetics


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