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The in vitro culture system outlined in this chapter allows for the delineation of events that occur during the development of CD34(+) hematopoietic precursor cells into mature KIR(+) human NK cells. This system can also be utilized to study the effects of gene overexpression or knockdown on the process of NK cell differentiation through retroviral(More)
MicroRNAs (miRs) have recently been identified as important regulators of gene expression at the posttranscriptional level. Although it has clearly been established that miRs influence the ontogeny of several immune cell lineages, the role of individual miRs during NK cell development has not been described. In this study, we show that miR-181 expression(More)
Natural killer (NK) cells were first identified for their capacity to reject bone marrow allografts in lethally irradiated mice without prior sensitization. Subsequently, human NK cells were detected and defined by their non-major histocompatibility complex (MHC)-restricted cytotoxicity toward transformed or virally infected target cells. Karre et al. later(More)
NK-cell function is regulated by the integration of signals received from activating and inhibitory receptors. Here we show that a novel immune receptor, T-cell Ig and mucin-containing domain-3 (Tim-3), is expressed on resting human NK cells and is up-regulated on activation. The NK92 NK-cell line engineered to overexpress Tim-3 showed a marked increase in(More)
The mechanisms underlying human natural killer (NK) cell phenotypic and functional heterogeneity are unknown. Here, we describe the emergence of diverse subsets of human NK cells selectively lacking expression of signaling proteins after human cytomegalovirus (HCMV) infection. The absence of B and myeloid cell-related signaling protein expression in these(More)
Killer Ig-like receptors (KIRs) are expressed in a variegated, clonally restricted fashion on NK cells and are important determinants of NK cell function. Although silencing of individual KIR genes is strongly correlated with the presence of CpG dinucleotide methylation within the promoter, the mechanism responsible for silencing has not been identified.(More)
The killer cell immunoglobulin-like receptor (KIR) repertoire of natural killer (NK) cells determines their ability to detect infected or transformed target cells. Although epigenetic mechanisms play a role in KIR gene expression, work in the mouse suggests that other regulatory elements may be involved at specific stages of NK-cell development. Here we(More)
It has recently been appreciated that NK cells exhibit many features reminiscent of adaptive immune cells. Considerable heterogeneity exists with respect to the ligand specificity of individual NK cells and as such, a subset of NK cells can respond, expand, and differentiate into memory-like cells in a ligand-specific manner. MHC I-binding inhibitory(More)
Upon maturation, natural killer (NK) cells acquire effector functions and regulatory receptors. New insights suggest a considerable functional heterogeneity and dynamic regulation of receptor expression in mature human NK cell subsets based on different developmental axes. Such processes include acquisition of lytic granules as well as regulation of(More)
Killer immunoglobulin-like receptors (KIRs) recognize class I major histocompatibility complex molecules and participate in the calibration of activation thresholds during human natural killer (NK) cell development. The stochastic expression pattern of the KIR repertoire follows the product rule, meaning that the probability of the coexpression of two or(More)