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Blood, 15 July 2007, Vol. 110, No. 2, pp. 578-586.
Prepublished online as a Blood First Edition Paper on March 28, 2007; DOI 10.1182/blood-2006-07-036228.


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Submitted July 18, 2006
Accepted March 16, 2007

A subpopulation of human peripheral blood NK cells that lacks inhibitory receptors for self MHC is developmentally immature

Sarah Cooley, Feng Xiao, Michelle Pitt, Michelle Gleason, Valarie McCullar, Tracy Bergemann, Karina L McQueen, Lisbeth A Guethlein, Peter Parham, and Jeffrey S Miller*

Division of Hematology, Oncology and Transplantation, University of Minnesota Cancer Center, Minneapolis, MN
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA

* Corresponding author; email: mille011{at}umn.edu.

How receptor acquisition correlates with the functional maturation of NK cells is poorly understood. We used quantitative real-time PCR assays to compare NKG2 and killer immunoglobulin-like receptor (KIR) gene expression in NK cells from allogeneic transplant recipients and their donors. Marked differences were observed in the NK subsets of recipients who had 8-fold more CD56bright cells, diminished KIR expression (except 2DL4) and increased NKG2A. In normal blood not all CD56dim cells express KIR, and a novel subpopulation of cells committed to the NK cell lineage was defined. These cells, which comprise 19.4 ± 2.8% of the CD56dim NK population in healthy donors, express the activating NKG2D and NKG2E receptors but no KIR or NKG2A. Although the CD56dim NKG2A-KIR- NK cells lack "at least one" inhibitory receptor for autologous MHC class I, they are not fully responsive, but functionally immature cells that exhibit poor cytotoxiciy and IFN-{gamma} production. Upon culture with IL-15 and a stromal cell line, CD56dim and CD56bright KIR- NK cells proliferate, express KIR and develop cytotoxicity and cytokine-producing potential. These findings have implications for the function of NK cells reconstituting after transplant and support a model for in vivo development in which CD56bright cells precede CD56dim cells.


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