Human Natural Killer cell expression of ULBP2 is associated with a mature functional phenotype

Hum Immunol. 2016 Oct;77(10):876-885. doi: 10.1016/j.humimm.2016.06.018. Epub 2016 Jun 24.

Abstract

NKG2D is an important activating receptor expressed on NK cells. Ligands (termed NKG2DL) for this receptor include ULBP1-6, MICA and MICB in humans; they are upregulated in stressed, cancerous or infected cells where they engage NKG2D to induce NK cell cytotoxicity and cytokine production. Expression of NKG2DL on effector cells has been described in mice and more recently in human cells. We confirm that NK cell lines and IL-2 stimulated primary human NK cells also express the NKG2DL, ULBP2. However, expression of ULBP2 was not a result of transfer from a non-NK cell to an NK cell and in contrast to recent reports we saw no evidence that ULBP2 expression targeted these NK cells for fratricide or for cytotoxicity by NKG2D-expressing, non-NK effector cells. ULBP2 expression was however linked to expression of mature CD57(+) NK cells. In particular, expression of ULBP2 was strongest on those NK cells that had evidence of recent activation and proliferation. We suggest that ULBP2 could be used to identify recently activated "mature" NK cells. Defining this phenotype would be useful for understanding the ontogeny on human NK cells.

Keywords: Human; NKG2D; Natural Killer cells; Phenotype; ULBP2.

MeSH terms

  • Animals
  • CD57 Antigens / metabolism
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation
  • Cytotoxicity, Immunologic
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Interleukin-2 / immunology
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation
  • Mice
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism*
  • Phenotype
  • Up-Regulation

Substances

  • CD57 Antigens
  • GPI-Linked Proteins
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-2
  • KLRK1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • ULBP2 protein, human