Affiliation:
1. From the Departments of Pediatrics and Medicine, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis; III Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technical University Munich, Germany; the Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands; and Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland.
Abstract
AbstractThe stages of human natural killer (NK) cell differentiation are not well established. Culturing CD34+ progenitors with interleukin 7 (IL-7), IL-15, stem cell factor (SCF), FLT-3L, and murine fetal liver cell line (EL08.1D2), we identified 2 nonoverlapping subsets of differentiating CD56+ cells based on CD117 and CD94 (CD117highCD94– and CD117low/–CD94+ cells). Both populations expressed CD161 and NKp44, but differed with respect to NKp30, NKp46, NKG2A, NKG2C, NKG2D, CD8, CD16, and KIR. Only the CD117low/– CD94+ population displayed cytotoxicity and interferon-γ production. Both populations arose from a single CD34+CD38– Lin– cell and their percentages changed over time in a reciprocal fashion, with CD117highCD94– cells predominating early and decreasing due to an increase of the CD117low/–CD94+ population. These 2 subsets represent distinct stages of NKcell differentiation, since purified CD117high CD94– cells give rise to CD117low/–CD94+ cells. The stromal cell line (EL08.1D2) facilitated the transition from CD117highCD94– to CD117low/–CD94+ via an intermediate phenotype (CD117lowCD94low/–). EL08.1D2 also maintained the mature phenotype, preventing the reversion of CD117low/–CD94+ cells to the intermediate (CD117lowCD94low/–) phenotype. An analogous population of CD56+CD117highCD94– cells was found in cord blood. The identified stages of NK-cell differentiation provide evidence for coordinated acquisition of HLA-specific inhibitory receptors (ie, CD94/NKG2A) and function in developing human NK cells.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Reference52 articles.
1. Trinchieri G. Biology of natural killer cells. Adv Immunol.1989;47: 187-376.
2. Moretta A, Bottino C, Vitale M, et al. Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol.2001;19: 197-223.
3. Vitale M, Della Chiesa M, Carlomagno S, et al. NK-dependent DC maturation is mediated by TNF{alpha} and IFN{gamma} released upon engagement of the NKp30 triggering receptor. Blood.2005;106: 566-571.
4. Cooper MA, Fehniger TA, Turner SC, et al. Human natural killer cells: a unique innate immunoregulatory role for the CD56(bright) subset. Blood.2001;97: 3146-3151.
5. Lotzova E, Savary CA. Human natural killer cell development from bone marrow progenitors: analysis of phenotype, cytotoxicity and growth. Nat Immun.1993;12: 209-217.
Cited by
131 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献