Specificity, tolerance and developmental regulation of natural killer cells defined by expression of class I‐specific Ly49 receptors

Raulet, David H.; Held, Werner; Correa, Isabel; Dorfman, Jeffrey R.; Wu, Ming-Fan; Corral, Laura G.

doi:10.1111/j.1600-065x.1997.tb00938.x

Cited by 210 publications

(206 citation statements)

References 46 publications

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“…Other immune examples of stochastic processes include the probabilistic expression of cytokines 5,6 and the combinatorial expression of natural killer cell receptors in a population 7 .…”

Section: Precedentmentioning

confidence: 99%

Why the immune system takes its chances with randomness

2014

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“…Other immune examples of stochastic processes include the probabilistic expression of cytokines 5,6 and the combinatorial expression of natural killer cell receptors in a population 7 .…”

Section: Precedentmentioning

confidence: 99%

Why the immune system takes its chances with randomness

2014

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“…3 So far, two phosphatases, namely SHP-1 and SHP-2, have been shown to interact with tyrosine-phosphorylated ITIMs of Ly49 and NKG2A receptors (6,7). An important role for SHP-1 in the inhibitory pathway of mature NK cells is evident from several studies.…”

mentioning

confidence: 99%

“…These belong to the Ly49 and CD94/NKG2 receptor families, members of which recognize distinct MHC class I molecules and sometimes discriminate alleles thereof (2)(3)(4)(5). While the majority of MHC class I receptors inhibit, some also activate NK cell function.…”

mentioning

confidence: 99%

Impaired Natural Killing of MHC Class I-Deficient Targets by NK Cells Expressing a Catalytically Inactive Form of SHP-1

Lowin-Kropf

Kunz

Beermann³

et al. 2000

The Journal of Immunology

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NK cell function is negatively regulated by MHC class I-specific inhibitory receptors. Transduction of the inhibitory signal involves protein tyrosine phosphatases such as SHP-1 (SH2-containing protein tyrosine phosphatase-1). To investigate the role of SHP-1 for NK cell development and function, we generated mice expressing a catalytically inactive, dominant-negative mutant of SHP-1 (dnSHP-1). In this paper we show that expression of dnSHP-1 does not affect the generation of NK cells even though MHC receptor-mediated inhibition is partially impaired. Despite this defect, these NK cells do not kill syngeneic, normal target cells. In fact dnSHP-1-expressing NK cells are hyporesponsive toward MHC-deficient target cells, suggesting that non-MHC-specific NK cell activation is significantly reduced. In contrast, these NK cells mediate Ab-dependent cell-mediated cytotoxicity and prevent the engraftment with β2-microglobulin-deficient bone marrow cells. A similar NK cell phenotype is observed in viable motheaten (mev) mice, which show reduced SHP-1 activity due to a mutation in the Shp-1 gene. In addition, NK cells in both mouse strains show a tendency to express more inhibitory MHC-specific Ly49 receptors. Our results demonstrate the importance of SHP-1 for the generation of functional NK cells, which are able to react efficiently to the absence of MHC class I molecules from normal target cells. Therefore, SHP-1 may play an as-yet-unrecognized role in some NK cell activation pathways. Alternatively, a reduced capacity to transduce SHP-1-dependent inhibitory signals during NK cell development may be compensated by the down-modulation of NK cell triggering pathways.

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“…During bone marrow (BM) maturation, NK cells acquire a number of inhibitory receptors such as the CD94-NKG2 complex and members of the Ly49 family (2), and it is thought that in the naive setting, signaling through the repertoire of inhibitory receptors specific for autologous MHC class I keeps NK cells in a quiescent state (3).…”

mentioning

confidence: 99%

NK Cell Maturation and Peripheral Homeostasis Is Associated with KLRG1 Up-Regulation

Huntington

Tabarias

Fairfax

et al. 2007

The Journal of Immunology

300

312

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NK cells are important for the clearance of tumors, parasites, and virus-infected cells. Thus, factors that control NK cell numbers and function are critical for the innate immune response. A subset of NK cells express the inhibitory killer cell lectin-like receptor G1 (KLRG1). In this study, we identify that KLRG1 expression is acquired during periods of NK cell division such as development and homeostatic proliferation. KLRG1+ NK cells are mature in phenotype, and we show for the first time that these cells have a slower in vivo turnover rate, reduced proliferative response to IL-15, and poorer homeostatic expansion potential compared with mature NK cells lacking KLRG1. Transfer into lymphopenic recipients indicate that KLRG1− NK cells are precursors of KLRG1+ NK cells and KLRG1 expression accumulates following cell division. Furthermore, KLRG1+ NK cells represent a significantly greater proportion of NK cells in mice with enhanced NK cell numbers such as Cd45−/− mice. These data indicate that NK cells acquire KLRG1 on their surface during development, and this expression correlates with functional distinctions from other peripheral NK cells in vivo.

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Specificity, tolerance and developmental regulation of natural killer cells defined by expression of class I‐specific Ly49 receptors

Cited by 210 publications

References 46 publications

Why the immune system takes its chances with randomness

Why the immune system takes its chances with randomness

Impaired Natural Killing of MHC Class I-Deficient Targets by NK Cells Expressing a Catalytically Inactive Form of SHP-1

NK Cell Maturation and Peripheral Homeostasis Is Associated with KLRG1 Up-Regulation

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