Cutting Edge: Inhibitory Functions of the Killer Cell Lectin-Like Receptor G1 Molecule During the Activation of Mouse NK Cells

Section: Resultsmentioning

confidence: 99%

Distinct Phenotype and Function of NK Cells in the Pancreas of Nonobese Diabetic Mice

Brauner¹,

Elemans²,

Lemos³

et al. 2010

“…These studies identified the fact that NK cells responding to MCMV acquired KLRG1, and these cells contained less intracellular IFN-␥ compared with the KLRG1 Ϫ population (12,25). This finding was extended by our recent report on NK subsets where Mac-1 ϩ CD27 Ϫ KLRG1 ϩ cells were found to produce poor levels of IFN-␥ following stimulation with IL-12 and IL-18, cytokines required for the NK cell expansion during MCMV infection (28) or when cocultured with dendritic cells (23).…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports suggest that KLRG1 expression may be regulated by cytokines such as IFN␣ (12). IL-12 and IL-18 are both potent proinflammatory cytokines capable of activating NK cells (27).…”

Section: Klrg1 Expression Is Induced By Cytokinesmentioning

confidence: 99%

“…KLRG1 is expressed on ϳ30% of NK cells in the spleen of naive C57BL/6 mice and between 50 and 80% of CD56 dim human NK cells (10,11). It is has previously been shown that NK cells expressing KLRG1 accumulate following murine CMV (MCMV) infection and that these cells are mature in cell surface phenotype and undergo apoptosis preferentially during NK cell contraction (12). Virus-experienced CD8 ϩ T cells and human effector/memory T cells can also express KLRG1 (11,13).…”

mentioning

confidence: 99%

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

Huntington

Tabarias

Fairfax

et al. 2007

293

312

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.

“…1A). Still, compared with NK cells from naive LN, TINK cells showed an altered phenotype that included upregulation of KLRG1 (capable of inhibiting NK cell effector functions [44]), Ly6C (associated with an inert state [45]), and CD25 (Supplemental Fig. 1B), the downregulation of activating receptors NKG2D and NKp46 (Supplemental Fig.…”

Section: Tumor-experienced Nk Cells Have An Altered Phenotype and Expmentioning

confidence: 99%

NK Cells Restrain Spontaneous Antitumor CD8+ T Cell Priming through PD-1/PD-L1 Interactions with Dendritic Cells

Iraolagoitia

Spallanzani

Torres

et al. 2016

Despite the classical function of NK cells in the elimination of tumor and of virus-infected cells, evidence for a regulatory role for NK cells has been emerging in different models of autoimmunity, transplantation, and viral infections. However, this role has not been fully explored in the context of a growing tumor. In this article, we show that NK cells can limit spontaneous cross-priming of tumor Ag-specific CD8+ T cells, leading to reduced memory responses. After challenge with MC57 cells transduced to express the model Ag SIY (MC57.SIY), NK cell–depleted mice exhibited a significantly higher frequency of SIY-specific CD8+ T cells, with enhanced IFN-γ production and cytotoxic capability. Depletion of NK cells resulted in a CD8+ T cell population skewed toward an effector memory T phenotype that was associated with enhanced recall responses and delayed tumor growth after a secondary tumor challenge with B16.SIY cells. Dendritic cells (DCs) from NK cell–depleted tumor-bearing mice exhibited a more mature phenotype. Interestingly, tumor-infiltrating and tumor-draining lymph node NK cells displayed an upregulated expression of the inhibitory molecule programmed death ligand 1 that, through interaction with programmed death-1 expressed on DCs, limited DC activation, explaining their reduced ability to induce tumor-specific CD8+ T cell priming. Our results suggest that NK cells can, in certain contexts, have an inhibitory effect on antitumor immunity, a finding with implications for immunotherapy in the clinic.