Natural killers

CD44 is a widely expressed cell adhesion molecule that binds to the extracellular matrix component, hyaluronan. However, this interaction is not constitutive in most immune cells at steady state, as the ability of CD44 to engage hyaluronan is highly regulated. While activated T cells and macrophages gain the ability to bind hyaluronan by CD44, the status in other immune cells is less studied. Here we found a percentage of murine eosinophils, natural killer and natural killer T cells were capable of interacting with hyaluronan at steady state...

Esophageal squamous cell carcinoma (ESCC) is an aggressive upper gastrointestinal cancer and effective treatments are limited. Previous studies reported that natural killer (NK) cells expanded by coculturing with K562-mb15-41BBL feeder cells, a genetically modified K562 leukemia cell line that expresses membrane-bound interleukin (IL)-15 and 41BBL ligand, were highly proliferative and highly cytotoxic. Here, we investigated the potential of expanded NK cells for ESCC treatment. We analyzed both genetic and surface expression levels of NKG2D ligands (NKG2DLs) in ESCC using publicly available microarray data sets and ESCC cell lines...

OBJECTIVE: Antibody responses are often impaired in old age and in HIV+ infection despite virologic control with antiretroviral therapy but innate immunologic determinants are not well understood. DESIGN: Monocytes and natural killer cells were examined for relationships to age, HIV infection and influenza vaccine responses. METHODS: Virologically suppressed HIV+ (n = 139) and HIV- (n = 137) participants classified by age as young (18-39 years), middle-aged (40-59 years) and old (≥60 years) were evaluated preinfluenza and postinfluenza vaccination...

Dysregulation of innate and adaptive immunity is increasingly being recognized as one of core characteristics of schizophrenia pathophysiology. Several studies have revealed that patients with schizophrenia present various alterations in the levels of distinct leukocyte subpopulations. However, studies addressing this point have provided mixed results. Therefore, in this study we translated a computational deconvolution algorithm in order to estimate counts of distinct leukocyte subpopulations in peripheral blood of patients with schizophrenia...

BACKGROUND: Inhibitory receptor programmed cell death protein-1 (PD-1) is upregulated on a variety of immune cells, including natural killer (NK) cells, during chronic virus infection and tumorigenesis. Blockade of PD-1 or its ligands produces durable clinical responses with tolerable side effects in patients with a broad spectrum of cancers. However, the underlying molecular mechanisms of how PD-1 regulates NK cell function remain poorly characterized. OBJECTIVE: We sought to determine what effect PD-1 signaling has on NK cells...

BACKGROUND: Several studies have demonstrated that allergen-specific immunotherapy (SIT) can be an effective treatment for atopic dermatitis (AD). However, there is no relevant mouse model to investigate the mechanism and validate the novel modality of SIT in AD. METHODS: NC/Nga mice with induced AD-like skin lesions received a subcutaneous injection of SIT (an extract of the house dust mite Dermatophagoides farinae [DfE]) or placebo for 5 weeks). Clinical and histological improvements of AD-like skin lesions were examined...

Slow immune reconstitution is a major obstacle to the successful use of allogeneic hematopoietic cell transplantation (allo-HCT). As matched sibling donor (MSD) allo-HCT is regarded as the gold standard, we evaluated the pace of immune reconstitution in 157 adult recipients of reduced-intensity conditioning followed by MSD peripheral blood HCT (n = 68) and compared these to recipients of umbilical cord blood (UCB; n = 89). At day 28, UCB recipients had fewer natural killer (NK) cells than MSD recipients, but thereafter, NK cell numbers (and their subsets) were higher in UCB recipients...

RATIONALE: Lung natural killer (NK) cells kill a greater percentage of autologous lung parenchymal cells in COPD than in non-obstructed smokers. To become cytotoxic, NKs require priming, typically by dendritic cells (DC), but whether priming occurs in the lungs in COPD is unknown. METHODS: We used lung tissue and in some cases peripheral blood from patients undergoing clinically-indicated resections to determine in vitro killing of CD326+ lung epithelial cells by isolated lung CD56+ NKs...

An emerging new paradigm is that immune cell activation is controlled by transient interactions between supramolecular assemblies of receptors and ligands. Current immunotherapy biologic pharmaceuticals that activate or desensitize NK cells are, however, individual molecules that do not replicate this nanoscale organization of proteins. Here, we use nanoscale graphene oxide (NGO) as a template to generate soluble nanoscale clusters of Natural Killer cell-activating antibodies. We control nanocluster size and molecular number to mimic reported values for cell surface proteins...

The liver has been characterized as a frontline lymphoid organ with complex immunological features such as liver immunity and liver tolerance. Liver tolerance plays an important role in liver diseases including acute inflammation, chronic infection, autoimmune disease, and tumors. The liver contains a large proportion of natural killer (NK) cells, which exhibit heterogeneity in phenotypic and functional characteristics. NK cell activation, well known for its role in the immune surveillance against tumor and pathogen-infected cells, depends on the balance between numerous activating and inhibitory signals...

The role of immune system in various bone pathologies, such as osteoporosis, osteoarthritis, and rheumatoid arthritis is now well established. This had led to the emergence of a modern field of systems biology called as osteoimmunology, an integrated research between fields of immunology and bone biology under one umbrella. Osteoporosis is one of the most common inflammatory bone loss condition with more than 200 million individuals affected worldwide. T helper (Th) cells along with various other immune cells are major players involved in bone homeostasis...

The critical role of angiogenesis in promoting tumor growth and metastasis is strongly established. However, tumors show considerable variation in angiogenic characteristics and in their sensitivity to antiangiogenic therapy. Tumor angiogenesis involves not only cancer cells but also various tumor-associated leukocytes (TALs) and stromal cells. TALs produce chemokines, cytokines, proteases, structural proteins, and microvescicles. Vascular endothelial growth factor (VEGF) and inflammatory chemokines are not only major proangiogenic factors but are also immune modulators, which increase angiogenesis and lead to immune suppression...

The location of intraepithelial lymphocytes (IEL) between epithelial cells, their effector memory, cytolytic and inflammatory phenotype positions them to kill infected epithelial cells and protect the intestine against pathogens. Human TCRαβ+ CD8αβ+ IEL have the dual capacity to recognize modified self via natural killer (NK) receptors (autoreactivity) as well as foreign antigen via the T cell receptor (TCR), which is accomplished in mouse by two cell subsets, the naturally occurring TCRαβ+ CD8αα+ and adaptively induced TCRαβ+ CD8αβ+ IEL subsets, respectively...

Aggressive natural killer-cell (NK-cell) leukemia (ANKL) is an extremely aggressive malignancy with dismal prognosis and lack of targeted therapies. Here, we elucidate the molecular pathogenesis of ANKL using a combination of genomic and drug sensitivity profiling. We study 14 ANKL patients using whole-exome sequencing (WES) and identify mutations in STAT3 (21%) and RAS-MAPK pathway genes (21%) as well as in DDX3X (29%) and epigenetic modifiers (50%). Additional alterations include JAK-STAT copy gains and tyrosine phosphatase mutations, which we show recurrent also in extranodal NK/T-cell lymphoma, nasal type (NKTCL) through integration of public genomic data...

Primitive nucleated erythroid cells in the bloodstream have long been suggested to be more similar to nucleated red cells of fish, amphibians, and birds than the red cells of fetal and adult mammals. Rainbow trout Ficoll-purified red blood cells (RBCs) cultured in vitro undergo morphological changes, especially when exposed to stress, and enter a new cell stage that we have coined shape-shifted RBCs (shRBCs). We have characterized these shRBCs using transmission electron microscopy (TEM) micrographs, Wright⁻Giemsa staining, cell marker immunostaining, and transcriptomic and proteomic evaluation...

BACKGROUND: Leukocyte count is closely associated with the risk of coronary artery disease (CAD). Levels of leukocyte subpopulations in CAD patients, however, remain largely unknown. METHODS: In the present study, we compared the distributions and counts of 16 leukocyte subpopulations between 40 CAD patients and 40 healthy controls using the CytoDiff flow cytometric system. RESULTS: Our results demonstrated significant increases in the frequencies and counts of all monocytes, immature granulocytes and B-lymphocytes in CAD patients, suggesting the levels of these leukocyte subpopulations may serve as potential biomarkers for diagnosis of CAD...

Introducing siRNA into human immune cells by an artificial delivery system continues to be a challenging issue. We previously developed a multifunctional envelope-type nanodevice (MEND) containing YSK12-C4, a fusogenic-cationic lipid, (YSK12-MEND) and succeeded in the efficient delivery of siRNA into human immune cell lines. Significant cytotoxicity, however, was observed at siRNA doses needed for gene silencing in NK-92 cells. NK-92 cells, a unique natural killer (NK) cell line, would be applicable for use in clinical NK therapy...

OBJECTIVE: To establish a novel method for ex vivo expansion of natural killer cells from human umbilical blood, so as to provide the basis for NK cell therapy. METHODS: Mononucleated cells from human umbilical blood were harvested and suspended in a serum-free medium containing 5% autologous plasma, recombinant human IL-15 (50 ng/ml) and hydrocortisone sodium succinate (5×10-8 mol/L) at a concentration of 1.5×106 /ml, then the cells were seeded into flasks pre-coated with heparin sodium (100 U/cm2 ) or/and anti-human CD16 antibody (1 µg/cm2 )...

OBJECTIVE: To develop an easy method to amplify natural killer (NK) cells by using mononuclear cells in vitro, so as to lay the basis for NK cell therapy. METHODS: Umbilical cord blood from 3 healthy full-term pregnant women was collected, and the peripheral blood mononuclear cells (PBMNC) were harvested by density gradient centrifugation. Each sample of PBMNC was divided into 3 groups: CD16mAb, CD3 mAb and CD16mAb+CD3mAb- groups. The culture flasks were pre-coated with CD16, CD3 or CD3 plus CD16 mAb...

We report that Histone Deacetylase 7 (HDAC7) controls the thymic effector programming of Natural Killer T (NKT) cells, and that interference with this function contributes to tissue-specific autoimmunity. Gain of HDAC7 function in thymocytes blocks both negative selection and NKT development, and diverts Vα14/Jα18 TCR transgenic thymocytes into a Tconv-like lineage. Conversely, HDAC7 deletion promotes thymocyte apoptosis and causes expansion of innate-effector cells. Investigating the mechanisms involved, we found that HDAC7 binds PLZF and modulates PLZF-dependent transcription...