CD4(+) NKG2D(+) T cells induce NKG2D down-regulation in natural killer cells in CD86-RAE-1ε transgenic mice.

Abstract

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.

• Authors: Zhijie Lin, Changrong Wang, Haizui Xia, Weiguang Liu, Weiming Xiao, Li Qian, Xiaoqin Jia, Yanbing Ding, Mingchun Ji, Weijuan Gong
• Journal: Immunology (Immunology) Vol. 141 Issue 3 Pg. 401-15 (Mar 2014) ISSN: 1365-2567 [Electronic] England
• PMID: 24708417 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 John Wiley & Sons Ltd.

Chemical References

• B7-2 Antigen
• Cd86 protein, mouse
• Klrk1 protein, mouse
• Ligands
• Membrane Proteins
• NK Cell Lectin-Like Receptor Subfamily K
• Raet1e protein, mouse
• Transforming Growth Factor beta
• Dextran Sulfate
• Poly I-C

Topics

• Animals
• B7-2 Antigen (genetics)
• CD4-Positive T-Lymphocytes (drug effects, immunology, metabolism)
• Cells, Cultured
• Colitis (chemically induced, immunology, metabolism, prevention & control)
• Dendritic Cells (immunology, metabolism)
• Dextran Sulfate
• Disease Models, Animal
• Down-Regulation
• Killer Cells, Natural (drug effects, immunology, metabolism)
• Ligands
• Melanoma, Experimental (immunology, metabolism)
• Membrane Proteins (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• NK Cell Lectin-Like Receptor Subfamily K (genetics, metabolism)
• Poly I-C (pharmacology)
• Promoter Regions, Genetic
• T-Lymphocytes, Regulatory (immunology, metabolism)
• Time Factors
• Transforming Growth Factor beta (metabolism)