Diversification of human NK cells: Lessons from deep profiling

J Leukoc Biol. 2018 Apr;103(4):629-641. doi: 10.1002/JLB.6RI0917-390R. Epub 2018 Jan 19.

Abstract

NK cells are innate lymphocytes with important roles in immunoregulation, immunosurveillance, and cytokine production. Originally defined on the functional basis of their "natural" ability to lyse tumor targets and thought to be a relatively homogeneous group of lymphocytes, NK cells possess a remarkable degree of phenotypic and functional diversity due to the combinatorial expression of an array of activating and inhibitory receptors. Diversification of NK cells is multifaceted: mechanisms of NK cell education that promote self-tolerance result in a heterogeneous repertoire that further diversifies upon encounters with viral pathogens. Here, we review the genetic, developmental, and environmental sources of NK cell diversity with a particular focus on deep profiling and single-cell technologies that will enable a more thorough and accurate dissection of this intricate and poorly understood lymphocyte lineage.

Keywords: NK cell; host-pathogen interaction; innate lymphoid cell; lymphocyte diversity; mass cytometry; single-cell technology.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Environment
  • Gene Expression Profiling*
  • Gene Expression Regulation*
  • Humans
  • Immunologic Memory
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*