Evidence for discrete stages of human natural killer cell differentiation in vivo

doi:10.1084/jem.20052507

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Published online 10 April 2006 doi:10.1084/jem.20052507
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JEM, Volume 203, Number 4, 1033-1043

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ARTICLE

Evidence for discrete stages of human natural killer cell differentiation in vivo

Aharon G. Freud¹^,2, Akihiko Yokohama³, Brian Becknell¹^,2, Melissa T. Lee⁵, Hsiaoyin C. Mao³, Amy K. Ferketich⁴, and Michael A. Caligiuri²^,3^,5^,6

¹ Medical Scientist Program, ² Integrated Biomedical Science Graduate Program, ³ Department of Molecular Virology, Immunology, and Medical Genetics, ⁴ Department of Epidemiology and Biometrics, ⁵ Division of Hematology/Oncology, Department of Internal Medicine, College of Medicine and Public Health, ⁶ The Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210

CORRESPONDENCE Michael A. Caligiuri: michael.caligiuri{at}osumc.edu

Human natural killer (NK) cells originate from CD34(+) hematopoieticprogenitor cells, but the discrete stages of NK cell differentiationin vivo have not been elucidated. We identify and functionallycharacterize, from human lymph nodes and tonsils, four NK celldevelopmental intermediates spanning the continuum of differentiationfrom a CD34(+) NK cell progenitor to a functionally mature NKcell. Analyses of each intermediate stage for CD34, CD117, andCD94 cell surface expression, lineage differentiation potentials,capacity for cytokine production and natural cytotoxicity, andETS-1, GATA-3, and T-BET expression provide evidence for a newmodel of human NK cell differentiation in secondary lymphoidtissues.

Abbreviations used: CB, cord blood; FasL, Fas ligand; FL, flt3ligand; FSC, forward scatter; HPC, hematopoietic progenitorcell; KIR, killer-cell immunoglobulin-like receptor; KL, c-kitligand; mRNA, messenger RNA; NKP, NK cell precursor; PB, peripheralblood; RLU, relative light units; SSC, side scatter; SLT, secondarylymphoid tissues; TRAIL, TNF-related apoptosis-inducing ligand.

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