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

Division of Hematology, Oncology and Transplantation, University of Minnesota Cancer Center, Minneapolis 55455, USA.
Blood (Impact Factor: 10.43). 08/2007; 110(2):578-86. DOI: 10.1182/blood-2006-07-036228
Source: PubMed

ABSTRACT How receptor acquisition correlates with the functional maturation of natural killer (NK) cells is poorly understood. We used quantitative real-time polymerase chain reaction (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 CD56(bright) cells, diminished KIR expression (except 2DL4), and increased NKG2A. In normal blood not all CD56(dim) 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 CD56(dim) NK population in healthy donors, express the activating NKG2D and NKG2E receptors but no KIR or NKG2A. Although the CD56(dim) NKG2A(-) KIR(-) NK cells lack "at least one" inhibitory receptor for autologous MHC class I, they are not fully responsive, but rather functionally immature cells with poor cytotoxicity and IFN-gamma production. Upon culture with IL-15 and a stromal cell line, CD56(dim) and CD56(bright) 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 transplantation and support a model for in vivo development in which CD56(bright) cells precede CD56(dim) cells.

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Available from: Tracy L Bergemann, Aug 26, 2015
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    • "Expression from individual KIR genes is independently regulated within each NK cell, and during NK cell development, a repertoire of cells is established, in which distinct NK cells stochastically express different members of the KIR family. In order to achieve functional competence, each NK cell must express at least one KIR family member that recognizes at least one of the expressed " self " MHC-I molecules (Anfossi et al., 2006;Cooley et al., 2007). To create further diversity, individuals in the human population inherit different haplotypes of KIR family members (Uhrberg et al., 1997), and most individuals express some KIR that do not recognize their own " self " MHC-I molecules. "
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