CD4(+) NKG2D(+) T cells induce NKG2D down-regulation in natural killer cells in CD86-RAE-1ε transgenic mice.
The binding of NKG2D to its ligands strengthens the cross-talk between natural killer (NK) cells and dendritic cells, particularly at early stages, before the initiation of the adaptive immune response. We found that retinoic acid early transcript-1ε (RAE-1ε), one of the ligands of NKG2D, was persistently expressed on antigen-presenting cells in a transgenic mouse model (pCD86-RAE-1ε). By contrast, NKG2D expression on NK cells, NKG2D-dependent cytotoxicity and tumour rejection, and dextran sodium sulphate-induced colitis were all down-regulated in this mouse model. The down-regulation of NKG2D on NK cells was reversed by stimulation with poly (I:C). The ectopic expression of RAE-1ε on dendritic cells maintained NKG2D expression levels and stimulated the activity of NK cells ex vivo, but the higher frequency of CD4(+) NKG2D(+) T cells in transgenic mice led to the down-regulation of NKG2D on NK cells in vivo. Hence, high levels of RAE-1ε expression on antigen-presenting cells would be expected to induce the down-regulation of NK cell activation by a regulatory T-cell subset.
Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China.
Zhijie
Z
Lin
Changrong
C
Wang
Haizui
H
Xia
Weiguang
W
Liu
Weiming
W
Xiao
Li
L
Qian
Xiaoqin
X
Jia
Yanbing
Y
Ding
Mingchun
M
Ji
Weijuan
W
Gong
D000818:Animals; D051940:B7-2 Antigen / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D015536:Down-Regulation; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008546:Melanoma, Experimental / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; C527086:Klrk1 protein, mouse; D008024:Ligands; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; C584972:Raet1e protein, mouse; D016212:Transforming Growth Factor beta; D016264:Dextran Sulfate; D011070:Poly I-C
NKG2D; natural killer; regulation; retinoic acid early transcript-1; transgenic mouse