TY - JOUR
T1 - Loss of NKG2D in murine NK cells leads to increased perforin production upon long-term stimulation with IL-2
AU - Prinz, Daniela
AU - Klein, Klara
AU - List, Julia
AU - Knab, Vanessa M
AU - Menzl, Ingeborg
AU - Leidenfrost, Nicoletta
AU - Heller, Gerwin
AU - Polić, Bojan
AU - Putz, Eva Maria
AU - Witalisz-Siepracka, Agnieszka
AU - Sexl, Veronika
AU - Gotthardt, Dagmar
N1 - Publisher Copyright:
© 2020 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2020/6
Y1 - 2020/6
N2 - 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.
AB - 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.
KW - Animals
KW - Cell Line, Tumor
KW - Immunity, Cellular/drug effects
KW - Interferon-gamma/genetics
KW - Interleukin-2/pharmacology
KW - Killer Cells, Natural/immunology
KW - Mice
KW - Mice, Knockout
KW - NK Cell Lectin-Like Receptor Subfamily K/genetics
KW - Pore Forming Cytotoxic Proteins/genetics
UR - http://www.scopus.com/inward/record.url?scp=85085960305&partnerID=8YFLogxK
U2 - 10.1002/eji.201948222
DO - 10.1002/eji.201948222
M3 - Journal article
C2 - 32052406
SN - 0014-2980
VL - 50
SP - 880
EP - 890
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 6
ER -