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

Immunology. 2014 Mar;141(3):401-15. doi: 10.1111/imm.12203.

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.

Keywords: NKG2D; natural killer; regulation; retinoic acid early transcript-1; transgenic mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • 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