title: Eomesodermin and T-bet mark developmentally distinct human natural killer cells.
abstract: Immaturity of the immune system of human fetuses and neonates is often invoked to explain their increased susceptibility to infection; however, the development of the fetal innate immune system in early life remains incompletely explored. We now show that the most mature NK cells found in adult (or postnatal) human circulation (CD94-CD16+) are absent during ontogeny. Human fetal NK cells were found to express the 2 signature T-box transcription factors essential for the development of all murine NK and NK-like cells, eomesodermin (Eomes) and T-bet. The single-cell pattern of Eomes and T-bet expression during ontogeny, however, revealed a stereotyped pattern of reciprocal dominance, with immature NK cells expressing higher amounts of Eomes and more mature NK cells marked by greater abundance of T-bet. We also observed a stereotyped pattern of tissue-specific NK cell maturation during human ontogeny, with fetal liver being more restrictive to NK cell maturity than fetal bone barrow, spleen, or lung. These results support the hypothesis that maturation of human NK cells has a discrete restriction until postnatal life, and provide a framework to better understand the increased susceptibility of fetuses and newborns to infection.
authors.affiliation: Department of Pediatrics.|Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Amélie
authors.initials: A
authors.lastname: Collins
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Nyanza
authors.initials: N
authors.lastname: Rothman
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Pediatrics.|Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Reiner
mesh_terms: D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D002454:Cell Differentiation; D004198:Disease Susceptibility / Q000276:immunology; D005333:Fetus / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D020825:T-Box Domain Proteins / Q000378:metabolism*; D000098815:T-bet Transcription Factor
chemical_list: D015703:Antigens, CD; C491199:EOMES protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor