Systemic NKG2D down-regulation impairs NK and CD8 T cell responses in vivo
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Systemic NKG2D down-regulation impairs NK and CD8 T cell responses in vivo. / Wiemann, Katrin; Mittrücker, Hans-Willi; Feger, Ute; Welte, Stefan A; Yokoyama, Wayne M; Spies, Thomas; Rammensee, Hans-Georg; Steinle, Alexander.
In: J IMMUNOL, Vol. 175, No. 2, 15.07.2005, p. 720-9.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Systemic NKG2D down-regulation impairs NK and CD8 T cell responses in vivo
AU - Wiemann, Katrin
AU - Mittrücker, Hans-Willi
AU - Feger, Ute
AU - Welte, Stefan A
AU - Yokoyama, Wayne M
AU - Spies, Thomas
AU - Rammensee, Hans-Georg
AU - Steinle, Alexander
PY - 2005/7/15
Y1 - 2005/7/15
N2 - The immunoreceptor NKG2D stimulates activation of cytotoxic lymphocytes upon engagement with MHC class I-related NKG2D ligands of which at least some are expressed inducibly upon exposure to carcinogens, cell stress, or viruses. In this study, we investigated consequences of a persistent NKG2D ligand expression in vivo by using transgenic mice expressing MHC class I chain-related protein A (MICA) under control of the H2-K(b) promoter. Although MICA functions as a potent activating ligand of mouse NKG2D, H2-K(b)-MICA mice appear healthy without aberrations in lymphocyte subsets. However, NKG2D-mediated cytotoxicity of H2-K(b)-MICA NK cells is severely impaired in vitro and in vivo. This deficiency concurs with a pronounced down-regulation of surface NKG2D that is also seen on activated CD8 T cells. As a consequence, H2-K(b)-MICA mice fail to reject MICA-expressing tumors and to mount normal CD8 T cell responses upon Listeria infection emphasizing the importance of NKG2D in immunity against tumors and intracellular infectious agents.
AB - The immunoreceptor NKG2D stimulates activation of cytotoxic lymphocytes upon engagement with MHC class I-related NKG2D ligands of which at least some are expressed inducibly upon exposure to carcinogens, cell stress, or viruses. In this study, we investigated consequences of a persistent NKG2D ligand expression in vivo by using transgenic mice expressing MHC class I chain-related protein A (MICA) under control of the H2-K(b) promoter. Although MICA functions as a potent activating ligand of mouse NKG2D, H2-K(b)-MICA mice appear healthy without aberrations in lymphocyte subsets. However, NKG2D-mediated cytotoxicity of H2-K(b)-MICA NK cells is severely impaired in vitro and in vivo. This deficiency concurs with a pronounced down-regulation of surface NKG2D that is also seen on activated CD8 T cells. As a consequence, H2-K(b)-MICA mice fail to reject MICA-expressing tumors and to mount normal CD8 T cell responses upon Listeria infection emphasizing the importance of NKG2D in immunity against tumors and intracellular infectious agents.
KW - Animals
KW - CD8-Positive T-Lymphocytes
KW - CHO Cells
KW - Cell Line, Tumor
KW - Coculture Techniques
KW - Cricetinae
KW - Cytotoxicity, Immunologic
KW - Down-Regulation
KW - Graft Rejection
KW - H-2 Antigens
KW - Histocompatibility Antigens Class I
KW - Immunity, Innate
KW - Killer Cells, Natural
KW - Listeriosis
KW - Lymphocyte Activation
KW - Lymphoma, T-Cell
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Inbred CBA
KW - Mice, Knockout
KW - Mice, Transgenic
KW - NK Cell Lectin-Like Receptor Subfamily K
KW - Receptors, Immunologic
KW - Receptors, Natural Killer Cell
M3 - SCORING: Journal article
C2 - 16002667
VL - 175
SP - 720
EP - 729
JO - J IMMUNOL
JF - J IMMUNOL
SN - 0022-1767
IS - 2
ER -