Gene expression in NKR-P1B+ versus Ly49s3+ rat NK cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Marit Inngjerdingen
PROVIDER: E-GEOD-20935 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:we compare NK cells in presence of activated CD8 T cells or not. Although both natural killer (NK) cells and CD8 T cells are capable of anti-tumor responses, Recombinase Activating Gene (RAG)-deficient mice, which have a normal component of NK cells, are incapable of rejecting the P815 mastocytoma tumor. We established a model where monoclonal CD8 T cell reactivity was restricted to the tumor antigen (Ag) P1A expressed on the P815 mastocytoma. Reconstitution of the RAG-deficient mice with these (TCRP1A) T cells conferred resistance to tumor growth selectively for the P1A-expressing, but not for a P1A-negative variant of P815. Nevertheless, TCRP1A CD8 T cells were efficient and necessary to promote the NK cell dependent rejection of P1A-negative tumors when both P1A-positive and -negative tumors were present at the same site. Gene expression profiling in NK cells infiltrating the P1A-positive, as compared to the P1A-negative tumor, in mice transferred with TCRP1A CD8 T cells established their acquisition of an activated effector phenotype. Help from CD8 T cells was provided locally, as it did not induce activation of NK cells present in a P1A-negative variant at a distant site, nor the rejection of this variant. These results illustrate a mechanism by which, in the face of immunoselection / editing, the synergy between specific anti-tumor Ag T cells and NK cells can contribute to the elimination of tumor cells whether or not they express the tumor Ag. This mechanism appears ineffective, however, once tumor variants lacking the tumor Ag are separated from the wild-type tumor, as would be the case in tumor metastasis.
2007-11-01 | E-MEXP-1284 | biostudies-arrayexpress
Project description:Human Natural Killer (NK) cells comprise two main subsets, CD56bright and CD56dim cells, that differ in function, phenotype and tissue localization. To further dissect the heterogeneity of CD56dim cells, we have performed transcriptome analysis and functional ex vivo characterization of human NK cell subsets according to the expression of markers related to differentiation, migration or competence. Here, we show for the first time that the ability to respond to cytokines or to activating receptors is mutually exclusive in almost all NK cells with the exception of CD56dim CD62L+ cells. Indeed, only these cells combine the ability to produce interferon (IFN)-gamma after cytokines and proliferate in vivo during viral infection with the capacity to kill and produce cytokines upon engagement of activating receptors. Therefore, CD56dim CD62L+ cells represent a unique subset of polyfunctional NK cells. Ex vivo analysis of their function, phenotype, telomere length, frequencies during ageing as well as transfer experiments of NK cell subsets into immunodeficient mice suggest that CD56dim CD62L+ cells represent an intermediate stage of NK cell maturation, which after restimulation can accomplish multiple tasks and further develop into terminally differentiated effectors. Gene expression profiles of FACSAria sorted CD3- CD56bright CD62L+, CD3- CD56dim CD62L+ and CD3- CD56dim CD62L- NK cells from human peripheral blood of three donors were compared using Affymetrix GeneChip Human Genome HG-U133_Plus_2. After total RNA extraction, reverse transcription, cDNA extraction, the biotinylated cRNA was transcribed, fragmented, and 15 µg cRNA hybridized in triplicates for each of the three groups to the GeneChip arrays. Group1: CD3- CD56bright CD62L+,.Group2: CD3- CD56dim CD62L+, Group3: CD3- CD56dim CD62L-. Lists of differentially regulated genes were created using High Performance Chip Data Analysis (HPCDA) with Bioretis database (http://www.bioretis-analysis.de). Worldwide data sharing is possible via Bioretis, please ask the authors.
2010-05-28 | E-GEOD-21774 | biostudies-arrayexpress
Project description:It is known that NK cells are a heterogeneous population of functionally distinct NK cell subsets. Here we report on different genomic, phenotypic and functional properties of four murine NK cell subsets distinguished by CD117 (c-kit), CD27 and CD11b expression. Gene expression was measured in NK cell subsets freshly sorted from murine C57Bl/6 splenocytes. Two to three different batches were analysed.
2016-04-01 | E-GEOD-45842 | biostudies-arrayexpress
Project description:As a starting point for exploring potential differences in gene expression between conventional NK and FcRγ-NK cells, and to screen for genes that might contribute to the enhanced CD16 responsiveness of g-NK cells, we performed gene expression profiling studies on sorted samples of NK cells. NKG2C, NCR, and KIR surface receptors were used to separate FcRγ- NK and conventional NK cells. Indicated subsets of NK cells were sorted from 4 individual donors using a two-way sorter. RNA extracted from the sorted enriched samples were treated with Dnase and analyzed by DNA microarray (Agilent).
2015-02-20 | E-GEOD-66124 | biostudies-arrayexpress
Project description:Natural Killer Gene Complex (NKC)-encoded immunomodulatory C-type lectin-like receptors (CTLR) include members of the NKRP1 and CLEC2 gene families, which constitute genetically linked receptor-ligand pairs and are thought to allow for NK cell-mediated immunosurveillance of stressed or infected tissues. The mouse CTLR Nkrp1g was previously shown to form several receptor-ligands pairs with the CLEC2 proteins Clr-d, Clr-f, and Clr-g, respectively. Recently, we demonstrated a gut-restricted expression of Clr-f on intestinal epithelial cells that is spatially matched by Nkrp1g on subsets of intraepithelial lymphocytes (Leibelt et al., 2015). We now investigated expression and ligand interaction of Nkrp1g in the splenic compartment, and found an exclusive expression of Nkrp1g on a small subset of NK cells that upregulates Nkrp1g after cytokine exposure. To further characterize NKrp1g+ NK cells, we performed microarray analysis of resting Nkrp1g+ versus Nkrp1g- splenic NK cells that were purified by FACsorting. Total RNA isolation was followed by an Affymetrix microarray analysis.
2017-11-21 | E-MTAB-6223 | biostudies-arrayexpress
Project description:Chronic lymphocytic leukemia (B-CLL) and small lymphocytic lymphoma (SLL) are part of the same disease classification but are defined by differential distribution of tumor cells. B-CLL is characterized by significant immune suppression and dysregulation but this is nottypical of patients with SLL. Natural killer cells (NK) are important mediators of immune function but have been relatively poorly studied in patients with B-CLL/SLL.
2016-09-30 | E-MTAB-4403 | biostudies-arrayexpress
Project description:Natural killer (NK) cells can be grouped into distinct subsets that are localized to different organs and exhibit different capacity to secrete cytokines and mediate cytotoxicity. Despite these hallmarks that reflect tissue-specific specialization in NK cells, little is known about the factors that control the development of these distinct subsets. The basic leucine zipper transcription factor nuclear factor interleukin 3 (Nfil3; E4bp4) is essential for bone marrow-derived NK cell development but it is not clear whether Nfil3 is equally important for all NK cell subsets nor how it induces NK lineage commitment. Here we show that Nfil3 is required for the formation of Eomesodermin (Eomes)-expressing NK cells, including conventional medullary and thymic NK cells, whereas TRAIL+ Eomes- NK cells develop independent of Nfil3. Loss of Nfil3 during the development of bone marrow-derived NK cells resulted in reduced expression of Eomes and, conversely, restoration of Eomes expression in Nfil3-/- progenitors rescued NK cell development and maturation. Collectively, these findings demonstrate that Nfil3 drives the formation of mature NK cell by inducing Eomes expression and reveal the differential requirements of NK cell subsets for Nfil3. RNA-sequencing of natural killer (NK) cell subsets
2014-05-07 | E-GEOD-54291 | biostudies-arrayexpress
Project description:Fragmented RNA cocktails from FACS sorted Human decidual NK cell, and peripheral blood CD56Bright and CD56Dim NK cells, previously hybridization to HGU95AV2 chips (Koopman et al J Exp Med. 2003 Oct 20;198(8):1201-1), were stored long term at -80C, thawed and hybridized to HG-U133B arrays. Transcriptome analysis of Human decidual NK cells and NK cells from peripheral blood using Affymetrix UGU133B arrays.
2016-04-06 | E-GEOD-79939 | biostudies-arrayexpress
Project description:Natural killer (NK) cells are lymphocytes that participate in immune responses through their cytotoxic activity and secretion of cytokines and chemokines. They can be activated by interaction with ligands on target cells or by soluble mediators such as cytokines. In addition, soluble HLA-G, a major histocompatibility complex molecule secreted by fetal trophoblast cells during early pregnancy, stimulates resting NK cells to secrete proinflammatory and proangiogenic factors. Human NK cells are abundant in uterus, where they remain after implantation. Soluble HLA-G is endocytosed into early endosomes of NK cells where its receptor, CD158d, initiates a signaling cascade through DNA-PKcs, Akt and NF-kB3. The physiological relevance of this endosomal signaling pathway, and how the fate and function of NK cells during early pregnancy is regulated, is unknown. Here we show that soluble agonists of CD158d trigger DNA damage response signaling and p21 (CIP1/WAF1) expression to promote senescence in primary NK cells. CD158d engagement resulted in morphological alterations in cell size and shape, chromatin remodeling, and survival in the absence of proliferation, all hallmarks of senescence. Microarray analysis revealed a senescence signature of upregulated genes upon sustained activation through CD158d. The proinflammatory and proangiogenic factors secreted by these metabolically active NK cells are part of a senescence associated secretory phenotype (SASP) that promoted tissue remodeling and angiogenesis as assessed by functional readouts of vascular permeability and endothelial cell tube formation. We propose that ligand-induced senescence is a molecular switch for the sustained activation of NK cells in response to soluble HLA-G for the purpose of remodeling the maternal vasculature in early pregnancy. Time series (4 hr, 16 hr, 64 hr) of NK cells treated with agonist (anti-CD158d mAb) or control. NK cells were from 4 donors.
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