title: A human CD34(+) subset resides in lymph nodes and differentiates into CD56bright natural killer cells.
abstract: In humans, T cells differentiate in thymus and B cells develop in bone marrow (BM), but the natural killer (NK) precursor cell(s) and site(s) of NK development are unclear. The CD56bright NK subset predominates in lymph nodes (LN) and produces abundant cytokines compared to the cytolytic CD56dim NK cell that predominates in blood. Here, we identify a novel CD34dimCD45RA(+) hematopoietic precursor cell (HPC) that is integrin alpha4beta7bright. CD34dimCD45RA(+)beta7bright HPCs constitute <1% of BM CD34(+) HPCs and approximately 6% of blood CD34(+) HPCs, but >95% of LN CD34(+) HPCs. They reside in the parafollicular T cell regions of LN with CD56bright NK cells, and when stimulated by IL-15, IL-2, or activated LN T cells, they become CD56bright NK cells. The data identify a new NK precursor and support a model of human NK development in which BM-derived CD34dimCD45RA(+)beta7bright HPCs reside in LN where endogenous cytokines drive their differentiation to CD56bright NK cells in vivo.
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Aharon G
authors.initials: AG
authors.lastname: Freud
authors.forename: Brian
authors.initials: B
authors.lastname: Becknell
authors.forename: Sameek
authors.initials: S
authors.lastname: Roychowdhury
authors.forename: Hsiaoyin C
authors.initials: HC
authors.lastname: Mao
authors.forename: Amy K
authors.initials: AK
authors.lastname: Ferketich
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Nuovo
authors.forename: Tiffany L
authors.initials: TL
authors.lastname: Hughes
authors.forename: Trent B
authors.initials: TB
authors.lastname: Marburger
authors.forename: John
authors.initials: J
authors.lastname: Sung
authors.forename: Robert A
authors.initials: RA
authors.lastname: Baiocchi
authors.forename: Martin
authors.initials: M
authors.lastname: Guimond
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
mesh_terms: D018952:Antigens, CD34 / Q000276:immunology* / Q000378:metabolism; D019002:CD56 Antigen; D002454:Cell Differentiation / Q000276:immunology*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018952:Antigens, CD34; D019002:CD56 Antigen