The Journal of Experimental Medicine
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Published online 10 April 2006 doi:10.1084/jem.20052507
Rockefeller University Press, 0022-1007 $8.00
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(+) hematopoietic progenitor cells, but the discrete stages of NK cell differentiation in vivo have not been elucidated. We identify and functionally characterize, from human lymph nodes and tonsils, four NK cell developmental intermediates spanning the continuum of differentiation from a CD34(+) NK cell progenitor to a functionally mature NK cell. Analyses of each intermediate stage for CD34, CD117, and CD94 cell surface expression, lineage differentiation potentials, capacity for cytokine production and natural cytotoxicity, and ETS-1, GATA-3, and T-BET expression provide evidence for a new model of human NK cell differentiation in secondary lymphoid tissues.

Abbreviations used: CB, cord blood; FasL, Fas ligand; FL, flt3 ligand; FSC, forward scatter; HPC, hematopoietic progenitor cell; KIR, killer-cell immunoglobulin-like receptor; KL, c-kit ligand; mRNA, messenger RNA; NKP, NK cell precursor; PB, peripheral blood; RLU, relative light units; SSC, side scatter; SLT, secondary lymphoid tissues; TRAIL, TNF-related apoptosis-inducing ligand.


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