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  • Humans
  • Previous studies in mice and humans have suggested an important role for CD8+ T cells in host defense to Mtb. (nih.gov)
  • If translatable to humans, these data suggest that NK cells may be critically important for deciding whether allergic eosinophilic airway disease will develop. (nih.gov)
  • These data define a T cell lineage that is present already in cord blood and represents as many as one in six circulating CD8(+) T cells in normal humans and a substantial fraction of tissue-infiltrating CD8(+) T cells in chronic inflammation. (ox.ac.uk)
  • target cell lysis
  • In this study, we selected the BAB281 monoclonal antibody (mAb) on the basis of its ability to trigger NK-mediated target cell lysis. (nih.gov)
  • Flow cytometry experiments with Qa-1(b) tetramers and NK target cell lysis assays demonstrated that CD94/NKG2A discriminates between Qa-1(b) complexes containing peptides with substitutions at nonanchor positions P4, P5, or P8. (nih.gov)
  • Mice
  • Moreover, systemic allergen-specific immunoglobulin (Ig)E and IgG2a levels and the number of IL-4 and interferon gamma-producing splenic cells were diminished in mice depleted of NK1.1(+) cells before the priming regime. (nih.gov)
  • CD1d1 mutant mice, deficient in NKT cells but with normal NK cells, developed lung tissue eosinophilia and allergen-specific IgE levels not different from those observed in wild-type mice. (nih.gov)
  • Mice deficient in gamma/delta T cells showed a mild attenuation of lung tissue eosinophilia in this model. (nih.gov)
  • Corresponding mice depleted of NK1.1+ cells exhibited a few scattered eosinophilic infiltrates only (b), or a complete absence of pulmonary inflammation (not shown). (nih.gov)
  • In contrast, corresponding mice depleted of NK1.1+ cells (groups 8 and 10) showed a clearly inhibited eosinophilia in lung tissue (Fig. 1, a and b). (nih.gov)
  • H) Number of BrdU positive cells in basal and uppermost two granular layers per cm epidermis of mice treated three times with TPA and injected with BrdU 24 hr before harvesting. (nih.gov)
  • When mice were deprived of NK cells by antibody treatment before immunization, they developed a more serious form of EAE associated with relapse. (nih.gov)
  • Aggravation of EAE by NK cell deletion was also seen in beta 2-microglobulin-/- (beta 2m-/-) mice, indicating that NK cells can play a regulatory role in a manner independent of CD8+ T cells or NK1.1+ T cells (NK-T cells). (nih.gov)
  • EAE passively induced by the MOG35-55-specific T cell line was also enhanced by NK cell deletion in B6, beta 2m-/-, and recombination activation gene 2 (RAG-2)-/- mice, indicating that the regulation by NK cells can be independent of T, B, or NK-T cells. (nih.gov)
  • ZB-1 T line cells (4 × 104 cells/well) were stimulated with MOG35-55 in the presence of x irradiated spleen cells (8 × 105 cells/well) from wild-type B6 (A) or β2m−/− mice (B). In each experiment, spleen cells from mice pretreated with control mAb (control) and those pretreated with anti-NK1.1 mAb (anti-NK1.1) were compared in their accessory function. (nih.gov)
  • First, spleen cells from NK cell-deleted mice were compared with those from control mice as accessory cells for ZB-1 line cells. (nih.gov)
  • The experiment showed that antigen-induced ZB-1 cell proliferation is enhanced when spleen cells were derived from NK-deleted mice. (nih.gov)
  • We obtained similar results not only with spleen cells from wild-type B6 mice, but also from β2m−/− mice (Fig. 9, A and B). These indicate that irradiated, spleen NK cells would inhibit antigen-induced Th1 proliferation. (nih.gov)
  • Polyomavirus (PyV) induces tumors in neonatally infected mice of susceptible strains and in adult mice with certain immune deficiencies, and CD8+ alphabeta T cells are regarded as the main effectors in anti-tumor immunity. (umassmed.edu)
  • Here we report that adult TCRbeta knockout (KO) mice that lack alphabeta but have gammadelta T cells remain tumor-free after PyV infection, whereas TCRbeta x delta KO mice that lack all T cells develop tumors. (umassmed.edu)
  • In addition, E26 mice, which lack NK and T cells, develop the tumors earlier than TCRbeta x delta KO mice. (umassmed.edu)
  • No significant difference was observed between OVA-challenged wild-type mice and γ/δ T cell-deficient mice. (nih.gov)
  • A moderate reduction, although statistically insignificant, of lung tissue eosinophilia was observed in OVA-challenged γ/δ T cell-deficient animals compared with corresponding wild-type mice (Fig. 7). (nih.gov)
  • Similarly, no significant difference in systemic levels of OVA-specific IgE was observed between OVA-challenged γ/δ T cell-deficient animals and corresponding wild-type mice (1,066.3 ± 314.5 and 2,567.4 ± 1,497.1 U/ml, respectively). (nih.gov)
  • Additionally, NK cells isolated from T. gondii -infected Ahr −/− mice had impaired expression of IL-10, which was associated with increased resistance to this infection. (jimmunol.org)
  • Consequently, mice in which T cells are unable to express IL-10 also develop immune-mediated tissue pathology when challenged with T. gondii ( 5 ). (jimmunol.org)
  • Additionally, IL-10 −/− RAG2 −/− mice reconstituted with CD4 + T cells that are capable of producing IL-10 survive T. gondii infection whereas their counterparts given IL-10 −/− CD4 + T cells do not ( 6 ). (jimmunol.org)
  • The biological relevance of innate sources of IL-10 was suggested by the finding that IL-10 −/− SCID mice, which lack B and T cells, exhibit improved survival following T. gondii infection compared with SCID mice ( 7 ). (jimmunol.org)
  • Here, by using novel transgenic mice carrying inducible Cre expressed under the control of Ncr1 gene, we demonstrated that two distinct long-lived NK cell subsets differentiate in a mouse model of cytomegalovirus (MCMV) infection. (nih.gov)
  • NK cells in NKp46-CreERT2 Tg mice carrying the Rosa26 -tdTomato allele or the Rosa26 -YFP alleles express tdTomato or YFP after tamoxifen administration. (nih.gov)
  • B-D) NKp46-CreERT2 Tg mice with a heterozygous Rosa26 -tdTomato allele were treated with tamoxifen for 5 consecutive days and immune cells were analyzed after the last tamoxifen administration. (nih.gov)
  • C57BL
  • We then analyzed all Rae-1 transcripts possibly generated by these promoters in C57BL/6 cell lines and tissues using RT-PCR and agarose gel analysis. (nih.gov)
  • subset
  • A-C) Beta-values for each methylation site identified by RRBS were averaged from two donors for each T or NK cell subset as indicated. (nih.gov)
  • We found that circulating iNKT cell proportions were significantly higher (P = 0·03) in patients with acute dengue when compared to healthy individuals and were predominantly of the CD4(+) subset. (ox.ac.uk)
  • Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties. (ox.ac.uk)
  • CD94/NKG2A complexes are also found on a subset of CD8+ T cells. (novusbio.com)
  • vitro
  • To obtain insights into the mechanism of NK cell-mediated regulation, we conducted in vitro experiments, assaying antigen-induced proliferation of ZB-1 cells in the presence of irradiated spleen cells as APCs. (nih.gov)
  • In vitro studies revealed that IL-12 stimulation increased NK cell AHR levels, and the AHR and AHR nuclear translocator were required for optimal production of IL-10. (jimmunol.org)
  • Antigens
  • Antigens are peptides or recombinant or native dependent on the production method.For cells, cell lines and tissues in culture till half confluency.Associated membrane protein types are lipopolysaccharide selective barriers. (anigenetics.com)
  • Importantly, unlike the NK cell antigens identified so far, the expression of p46 was strictly confined to NK cells. (nih.gov)
  • infection
  • RAE-1 is overexpressed in tumor cell lines and its expression is induced after viral infection and genotoxic stress. (nih.gov)
  • Human congenital infection with Trypanosoma cruzi induces phenotypic and functional modifications of cord blood NK cells. (ac.be)
  • Recently, it was shown that memory-like features can be observed in NK cell subsets after CMV infection. (nih.gov)
  • NK cells are also a source of IL-10 in other murine models of infection, as NK cell IL-10 promotes increased parasite burdens during visceral leishmaniasis and limits the magnitude of the CD8 + T cell response during murine CMV infection ( 8 - 10 ). (jimmunol.org)
  • Expansion of highly activated invariant natural killer T cells with altered phenotype in acute dengue infection. (ox.ac.uk)
  • In order to characterize further their role in dengue infection, we investigated the proportion of iNKT cells and their phenotype in adult patients with acute dengue infection. (ox.ac.uk)
  • Therefore, our data suggest that in acute dengue infection there is an expansion of highly activated CD4(+) iNKT cells, with reduced expression of CD161 markers. (ox.ac.uk)
  • Because previous studies have implicated NK cells in the control of MCMV predominantly in the liver and spleen and early during infection, viral titers in these organs were determined on day 3 after infection. (nih.gov)
  • synapse
  • Acquisition of MICA from target cells was dependent on cell contact and occurred after accumulation of MICA at the immunological synapse. (ox.ac.uk)
  • Dendritic Cells
  • T helper 17 cells (T(H)-17) represent a lineage of effector T cells critical in host defence and autoimmunity.Secretion of IL-1β, IL-23 and IL-6 by monocyte derived dendritic cells (MoDCs), were quantified by ELISA assay.These findings further support the central role of IL-1β in the differentiation of T(H)17 in human inflammatory conditions. (nih.gov)
  • Secretion of IL-1β, IL-23 and IL-6 by monocyte derived dendritic cells (MoDCs), were quantified by ELISA assay. (nih.gov)
  • Depletion
  • Depletion of NK1.1(+) cells during the challenge period only did not influence pulmonary eosinophilic inflammation.Taken together, these findings suggest a critical role of NK cells, but not of NKT cells, for the development of allergen-induced airway inflammation, and that this effect of NK cells is exerted during the immunization.These observations are also compatible with a pathogenic role for the increased NK cell activity observed in human asthma. (nih.gov)
  • We demonstrate here that depletion of NK1.1(+) cells (NK cells and NKT cells) before immunization inhibits pulmonary eosinophil and CD3(+) T cell infiltration as well as increased levels of interleukin (IL)-4, IL-5, and IL-12 in bronchoalveolar lavage fluid in a murine model of allergic asthma. (nih.gov)
  • Depletion of NK1.1(+) cells during the challenge period only did not influence pulmonary eosinophilic inflammation. (nih.gov)
  • These IL-10 reporter + NK cells expressed high levels of the IL-12 target genes T-bet, KLRG1, and IFN-γ, and IL-12 depletion abrogated reporter expression. (jimmunol.org)
  • NK1.1
  • Tumor rejection was dependent on CD8(+) and NK1.1(+) cells but occurred irrespective of the presence of CD4(+) T cells. (nih.gov)
  • Effect of depleting NK1.1+ cells before immunization on the development of eosinophilic pulmonary inflammation. (nih.gov)
  • Numbers in the upper right hand corner correspond to percentage of NK1.1+ cells that are tetramer positive. (nih.gov)
  • specificity
  • To confirm the specificity of NK cell staining, a parallel experiment was performed with transfectants expressing high levels of CD94/NKG2A. (nih.gov)
  • NKG2C
  • The accessibility of the CNS1 was required to enhance IFN-γ transcriptional activity in response to NKG2C and 2B4 engagement, which led to consistent IFN-γ production in NKG2C(hi) NK cells. (nih.gov)
  • In order to understand whether IFNG CNS1 demethylation was part of a broader epigenetic remodeling occurring in NKG2Chi expansions from HCMV+ individuals, we performed RRBS-based global methylation analysis of CD57+ NKG2Chi, CD57+ NKG2C− and CD57− NKG2C− NK cells in comparison with CD8+ memory and CD4+ TH1 cells as well as with CD8+ or CD4+ naïve T cells isolated from the same HCMV+ individuals. (nih.gov)
  • Differentiation
  • These findings reveal that NK cells are capable of differentiation into distinct long-lived subsets with different functional properties. (nih.gov)
  • May play a regulatory role in differentiation and survival of NK cells. (cusabio.com)
  • Spleen
  • and non-NK, non-T, and non-B cells (NKp46 − TCRβ − B220 − , predominantly myeloid cells) in the spleen. (nih.gov)
  • recognition
  • However, MCMV has evolved mechanisms to elude recognition and clearance by NK cells. (nih.gov)
  • We hypothesized that NK cell recognition of virus-infected cells may be impaired by m155. (nih.gov)
  • The type-II transmembrane glycoprotein CD94 covalently associates with C-type lectins of the NKG2 family to yield heterodimers important in NK cell recognition of class I MHC molecules. (novusbio.com)
  • binds
  • As previously reported 23, tetramers generated from Qa-1b folded with Qdm peptide bind to 40-50% of splenic NK cells (Fig. 5 A). Staining with tetramers containing the Dk leader sequence, which contains Val instead of Ala at P3, was somewhat reduced compared with Qdm, yet a substantial fraction of NK cells clearly binds this reagent. (nih.gov)
  • bone marrow
  • C) Expression of tdTomato in NK precursor cells (TCRβ − CD19 − CD11b − DX5 − NKp46 − CD122 + ) and immature (CD11b − CD27 + ), intermediate (CD11b + CD27 + ), and mature (CD11b + CD27 + ) NK cells (TCRβ − CD19 − DX5 + NKp46 + ) in the bone marrow. (nih.gov)
  • Participates in NK cell-mediated bone marrow graft rejection. (cusabio.com)
  • vivo
  • C-D) Ex-vivo analysis of circulating CCR6+ (panel B) and CD161+ (panel C) memory T cells (CD4+CD45RA−) in the same three subgroups. (nih.gov)
  • RRBS-based global methylation analysis of NK cell and T cell subsets.Genomic DNA of ex vivo FACS sorted NK and T cell subsets was analyzed for CpG methylation by RRBS. (nih.gov)
  • The functionality of iNKT cells in patients was investigated by both interferon (IFN)-γ and interleukin (IL)-4 ex-vivo enzyme-linked immunospot (ELISPOT) assays following stimulation with alpha-galactosyl-ceramide (αGalCer). (ox.ac.uk)
  • effector
  • The effector target ratio was 20:1 against P815 target cells and 10:1 against K562 target cells. (nih.gov)
  • T helper 17 cells (T(H)-17) represent a lineage of effector T cells critical in host defence and autoimmunity. (nih.gov)
  • Taken together, we conclude that NK cells are an important regulator for EAE in both induction and effector phases. (nih.gov)
  • Expression of CD94/NKG2 heterodimers may regulate cell survival and effector functions. (novusbio.com)
  • Thus
  • Thus, our data identify epigenetic imprinting of the IFNG locus as selective hallmark and crucial mechanism driving strong and stable IFN-γ expression in HCMV-specific NK cell expansions, providing a molecular basis for the regulation of adaptive features in innate cells. (nih.gov)
  • Thus, ULBPs and MICA are expressed in lipid rafts at the cell surface. (ox.ac.uk)
  • cytolytic
  • Upon mAb-mediated cross-linking, p46 molecules induced strong cell triggering leading to [Ca2+]i increases, lymphokine production, and cytolytic activity both in resting NK cells and NK cell clones. (nih.gov)
  • p46-mediated triggering of cytolytic activity in fresh peripheral blood NK cells. (nih.gov)
  • for cytolytic activity against 51Cr-labeled K562 target cells in the absence of added mAbs. (nih.gov)
  • These cells were used for FACS® analysis of CD3-depleted populations (see Fig. 3) and for cytolytic activity against K562 and P815 target cells (see Fig. 6 a). (nih.gov)
  • In another set of experiments, PBMCs were stained for both anti-CD3 and anti-p46 mAb and subsequently cells lacking the expression of p46 or CD3 or both markers (CD3−, p46−) were sorted and analyzed for cytolytic activity against K562 target cells (see Fig. 6 b). (nih.gov)
  • cytomegalovirus
  • Among innate cells, NK cells play a crucial role in the defense against cytomegalovirus (CMV) and represent the main source of IFN-γ. (nih.gov)
  • This randomized phase II trial studies the safety and how well multi-peptide cytomegalovirus ( CMV )-modified vaccinia Ankara (MVA) vaccine works in reducing CMV complications in patients previously infected with CMV and are undergoing a donor hematopoietic cell transplant. (clinicaltrials.gov)
  • Surface
  • BAB281 identified a novel NK cell-specific surface molecule of 46 kD (p46) that is expressed by all resting or activated NK cells. (nih.gov)
  • Electron microscopy reveals constitutive clusters of ULBP at the cell surface. (ox.ac.uk)
  • antiviral
  • This may help to reduce both CMV complications and reduce the need for antiviral drugs in patients undergoing a donor hematopoietic cell transplant. (clinicaltrials.gov)