Human NK cell development: One road or many?

Research output: Contribution to journalArticle

Abstract

CD3 CD56+ NK cells develop from CD34+ hematopoietic progenitors (HPCs) in vivo, and this process can be recapitulated in vitro. The prevailing model is that human NK cell development occurs along a continuum whereby common lymphocyte progenitors (CLPs) gradually downregulate CD34 and upregulate CD56. Acquisition of CD94 marks commitment to the CD56bright stage, and CD56bright NK cells subsequently differentiate into CD56dim NK cells that upregulate CD16 and killer immunoglobulin-like receptors (KIR). Support for this linear model comes from analyses of cell populations in secondary lymphoid tissues and in vitro studies of NK cell development from HPCs. However, several lines of evidence challenge this linear model and suggest a more branched model whereby different precursor populations may independently develop into distinct subsets of mature NK cells. A more definitive understanding of human NK cell development is needed to inform in vitro differentiation strategies designed to generate NK cells for immunotherapy. In this review, we summarize current evidence supporting the linear and branched models of human NK cell development and the challenges associated with reaching definitive conclusions.

Original languageEnglish (US)
Article numberArticle 2078
JournalFrontiers in immunology
Volume10
Issue numberAUG
DOIs
StatePublished - Jan 1 2019

Fingerprint

Natural Killer Cells
Linear Models
Up-Regulation
KIR Receptors
Lymphoid Tissue
Immunotherapy
Population
Down-Regulation
Lymphocytes
In Vitro Techniques

Keywords

  • Adaptive
  • Development
  • Differentiation
  • Immune
  • Innate
  • NK cell
  • Precursor
  • Progenitor

PubMed: MeSH publication types

  • Journal Article
  • Review

Cite this

Human NK cell development : One road or many? / Cichocki, Frank; Grzywacz, Bartosz; Miller, Jeffrey S.

In: Frontiers in immunology, Vol. 10, No. AUG, Article 2078, 01.01.2019.

Research output: Contribution to journalArticle

@article{d8efd2dbae054f4791faeda9a54ea7bd,
title = "Human NK cell development: One road or many?",
abstract = "CD3− CD56+ NK cells develop from CD34+ hematopoietic progenitors (HPCs) in vivo, and this process can be recapitulated in vitro. The prevailing model is that human NK cell development occurs along a continuum whereby common lymphocyte progenitors (CLPs) gradually downregulate CD34 and upregulate CD56. Acquisition of CD94 marks commitment to the CD56bright stage, and CD56bright NK cells subsequently differentiate into CD56dim NK cells that upregulate CD16 and killer immunoglobulin-like receptors (KIR). Support for this linear model comes from analyses of cell populations in secondary lymphoid tissues and in vitro studies of NK cell development from HPCs. However, several lines of evidence challenge this linear model and suggest a more branched model whereby different precursor populations may independently develop into distinct subsets of mature NK cells. A more definitive understanding of human NK cell development is needed to inform in vitro differentiation strategies designed to generate NK cells for immunotherapy. In this review, we summarize current evidence supporting the linear and branched models of human NK cell development and the challenges associated with reaching definitive conclusions.",
keywords = "Adaptive, Development, Differentiation, Immune, Innate, NK cell, Precursor, Progenitor",
author = "Frank Cichocki and Bartosz Grzywacz and Miller, {Jeffrey S.}",
year = "2019",
month = "1",
day = "1",
doi = "10.3389/fimmu.2019.02078",
language = "English (US)",
volume = "10",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
number = "AUG",

}

TY - JOUR

T1 - Human NK cell development

T2 - One road or many?

AU - Cichocki, Frank

AU - Grzywacz, Bartosz

AU - Miller, Jeffrey S.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - CD3− CD56+ NK cells develop from CD34+ hematopoietic progenitors (HPCs) in vivo, and this process can be recapitulated in vitro. The prevailing model is that human NK cell development occurs along a continuum whereby common lymphocyte progenitors (CLPs) gradually downregulate CD34 and upregulate CD56. Acquisition of CD94 marks commitment to the CD56bright stage, and CD56bright NK cells subsequently differentiate into CD56dim NK cells that upregulate CD16 and killer immunoglobulin-like receptors (KIR). Support for this linear model comes from analyses of cell populations in secondary lymphoid tissues and in vitro studies of NK cell development from HPCs. However, several lines of evidence challenge this linear model and suggest a more branched model whereby different precursor populations may independently develop into distinct subsets of mature NK cells. A more definitive understanding of human NK cell development is needed to inform in vitro differentiation strategies designed to generate NK cells for immunotherapy. In this review, we summarize current evidence supporting the linear and branched models of human NK cell development and the challenges associated with reaching definitive conclusions.

AB - CD3− CD56+ NK cells develop from CD34+ hematopoietic progenitors (HPCs) in vivo, and this process can be recapitulated in vitro. The prevailing model is that human NK cell development occurs along a continuum whereby common lymphocyte progenitors (CLPs) gradually downregulate CD34 and upregulate CD56. Acquisition of CD94 marks commitment to the CD56bright stage, and CD56bright NK cells subsequently differentiate into CD56dim NK cells that upregulate CD16 and killer immunoglobulin-like receptors (KIR). Support for this linear model comes from analyses of cell populations in secondary lymphoid tissues and in vitro studies of NK cell development from HPCs. However, several lines of evidence challenge this linear model and suggest a more branched model whereby different precursor populations may independently develop into distinct subsets of mature NK cells. A more definitive understanding of human NK cell development is needed to inform in vitro differentiation strategies designed to generate NK cells for immunotherapy. In this review, we summarize current evidence supporting the linear and branched models of human NK cell development and the challenges associated with reaching definitive conclusions.

KW - Adaptive

KW - Development

KW - Differentiation

KW - Immune

KW - Innate

KW - NK cell

KW - Precursor

KW - Progenitor

UR - http://www.scopus.com/inward/record.url?scp=85072018117&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072018117&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2019.02078

DO - 10.3389/fimmu.2019.02078

M3 - Article

C2 - 31555287

AN - SCOPUS:85072018117

VL - 10

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

IS - AUG

M1 - Article 2078

ER -