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Sökning: WFRF:(Cardell M.)

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  • Cossarizza, A., et al. (författare)
  • Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
  • 2019
  • Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
  • Tidskriftsartikel (refereegranskat)abstract
    • These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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  • Bachert, C., et al. (författare)
  • Important research questions in allergy and related diseases: 3-chronic rhinosinusitis and nasal polyposis - a GA(2)LEN study
  • 2009
  • Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 64:4, s. 520-533
  • Forskningsöversikt (refereegranskat)abstract
    • Chronic rhinosinusitis is one of the most common health care challenges, with significant direct medical costs and severe impact on lower airway disease and general health outcomes. The diagnosis of chronic rhinosinusitis (CRS) currently is based on clinical signs, nasal endoscopy and CT scanning, and therapeutic recommendations are focussing on 2 classes of drugs, corticosteroids and antibiotics. A better understanding of the pathogenesis and the factors amplifying mucosal inflammation therefore seems to be crucial for the development of new diagnostic and therapeutic tools. In an effort to extend knowledge in this area, the WP 2.7.2 of the GA(2)LEN network of excellence currently collects data and samples of 1000 CRS patients and 250 control subjects. The main objective of this project is to characterize patients with upper airway disease on the basis of clinical parameters, infectious agents, inflammatory mechanisms and remodeling processes. This collaborative research will result in better knowledge on patient phenotypes, pathomechanisms, and subtypes in chronic rhinosinusitis. This review summarizes the state of the art on chronic rhinosinusitis and nasal polyposis in different aspects of the disease. It defines potential gaps in the current research, and points to future research perspectives and targets.
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  • Tatituri, R. V. V., et al. (författare)
  • Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs
  • 2013
  • Ingår i: Proceedings of the National Academy of Science of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:5, s. 1827-1832
  • Tidskriftsartikel (refereegranskat)abstract
    • CD1d-restricted natural killer T (NKT) cells include two major subgroups. The most widely studied are V alpha 14J alpha 18(+) invariant NKT (iNKT) cells that recognize the prototypical alpha-galactosylceramide antigen, whereas the other major group uses diverse T-cell receptor (TCR) alpha-and beta-chains, does not recognize alpha-galactosylceramide, and is referred to as diverse NKT (dNKT) cells. dNKT cells play important roles during infection and autoimmunity, but the antigens they recognize remain poorly understood. Here, we identified phosphatidylglycerol (PG), diphosphatidylglycerol (DPG, or cardiolipin), and phosphatidylinositol from Mycobacterium tuberculosis or Corynebacterium glutamicum as microbial antigens that stimulated various dNKT, but not iNKT, hybridomas. dNKT hybridomas showed distinct reactivities for diverse antigens. Stimulation of dNKT hybridomas by microbial PG was independent of Toll-like receptor-mediated signaling by antigen-presenting cells and required lipid uptake and/or processing. Furthermore, microbial PG bound to CD1d molecules and plate-bound PG/CD1d complexes stimulated dNKT hybridomas, indicating direct recognition by the dNKT cell TCR. Interestingly, despite structural differences in acyl chain composition between microbial and mammalian PG and DPG, lipids from both sources stimulated dNKT hybridomas, suggesting that presentation of microbial lipids and enhanced availability of stimulatory self-lipids may both contribute to dNKT cell activation during infection.
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  • Clark, K., et al. (författare)
  • Structure-Function Implications of the Ability of Monoclonal Antibodies Against alpha-Galactosylceramide-CD1d Complex to Recognize beta-Mannosylceramide Presentation by CD1d
  • 2019
  • Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • iNKT cells are CD1d-restricted T cells recognizing lipid antigens. The prototypic iNKT cell-agonist alpha-galactosylceramide (alpha-GalCer) alongside compounds with similar structures induces robust proliferation and cytokine production of iNKT cells and protects against cancer in vivo. Monoclonal antibodies (mAbs) that detect CD1d-alpha-GalCer complexes have provided critical information for understanding of antigen presentation of iNKT cell agonists. Although most iNKT cell agonists with antitumor properties are alpha-linked glycosphingolipids that can be detected by anti-CD1d-alpha-GalCer mAbs, beta-ManCer, a glycolipid with a beta-linkage, induces strong antitumor immunity via mechanisms distinct from those of alpha-GalCer. In this study, we unexpectedly discovered that anti-CD1d-alpha-GalCer mAbs directly recognized beta-ManCer-CD1d complexes and could inhibit beta-ManCer stimulation of iNKT cells. The binding of anti-CD1d-alpha-GalCer mAb with beta-ManCer-CD1d complexes was also confirmed by plasmon resonance and could not be explained by alpha-anomer contamination. The binding of anti-CD1d-alpha-GalCer mAb was also observed with CD1d loaded with another beta-linked glycosylceramide, beta-GalCer (C26:0). Detection with anti-CD1d-alpha-GalCer mAbs indicates that the interface of the beta-ManCer-CD1d complex exposed to the iNKT cell TCR can assume a structure like that of CD1d-alpha-GalCer, despite its disparate carbohydrate structure. These results suggest that certain beta-linked monoglycosylceramides can assume a structural display similar to that of CD1d-alpha-GalCer and that the data based on anti-CD1d-alpha-GalCer binding should be interpreted with caution.
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  • Senti, Gabriela, et al. (författare)
  • Intralymphatic Immunotherapy : Update and Unmet Needs.
  • 2019
  • Ingår i: International Archives of Allergy and Immunology. - : S. Karger. - 1018-2438 .- 1423-0097. ; 178:2, s. 141-149
  • Forskningsöversikt (refereegranskat)abstract
    • Allergen-specific immunotherapy (AIT) is the only allergy treatment that confers long-term symptom amelioration for patients suffering from allergy. The most frequently used allergen application route is subcutaneous injection (SCIT), commonly taken as the gold standard, followed by sublingual (SLIT) or oral (OIT) application of allergen preparations. This is an up-to-date review of the clinical evidence for a novel route of allergen application, i.e., directly into lymph nodes - intralymphatic immunotherapy (ILIT). The major advantages of ILIT over the current AIT approaches are its short duration and the low allergen doses administered. The whole treatment consists of merely 3 ultrasound-guided injections into inguinal lymph nodes 1 month apart. While the number of patients included in randomised controlled trials is still limited, the clinical results for ILIT are encouraging, but more clinical trials are needed, as well as more preclinical work for optimising formulations.
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  • Benson, Mikael, 1954, et al. (författare)
  • DNA microarray analysis of chromosomal susceptibility regions to identify candidate genes for allergic disease: A pilot study
  • 2004
  • Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 124:7, s. 813-819
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective-To examine whether DNA microarray analysis of chromosomal susceptibility regions for allergy can help to identify candidate genes. Material and Methods-Nasal biopsies were obtained from 23 patients with allergic rhinitis and 12 healthy controls. RNA was extracted from the biopsies and pooled into three patient and three control pools. These were then analysed in duplicate with DNA microarrays containing 12626 genes. Candidate genes were further examined in nasal biopsies (real-time polymerase chain reaction) and blood samples (single nucleotide polymorphisms) from other patients with allergic rhinitis and from controls. Results-A total of 37 differentially expressed genes were identified according to criteria involving both the size and consistency of the gene expression levels. The chromosomal location of these genes was compared with the chromosomal susceptibility regions for allergic disease. Using a statistical method, five genes were identified in these regions, including serine protease inhibitor, Kazal type, 5 (SPINK5) and HLA-DRB2. The relevance of these genes was examined in other patients with allergic rhinitis and in controls; none of the genes were differentially expressed in nasal biopsies. Moreover, no association between allergic rhinitis and SPINK5 polymorphisms was found, at either the genotype or haplotype level. Conclusions-DNA microarray analysis of chromosomal susceptibility regions did not lead to identification of candidate genes that could be validated in a new material. However, because gene polymorphisms may cause differential gene expression, further studies, including validation data, are needed to examine this approach.
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  • Ekman, A. -K., et al. (författare)
  • Systemic Up-Regulation of TLR4 Causes Lipopolysaccharide-Induced Augmentation of Nasal Cytokine Release in Allergic Rhinitis
  • 2012
  • Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 159:1, s. 6-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Allergic rhinitis is a systemic disorder, and it is clinically well recognized that it can be aggravated by infection. Activation of the innate immune system constitutes a critical element in the process. Toll-like receptors (TLRs) comprise a part of the innate immune system, and lipopolysaccharide (LPS)-induced activation of TLR4 represents bacterial-induced interactions in various model systems. The present study examines how TLR2 and TLR4 expression is affected by symptomatic allergic rhinitis, and if LPS added upon allergen affects nasal cytokine release. Methods: In patients with pollen-induced allergic rhinitis and healthy non-allergic volunteers, nasal lavage (NAL), peripheral blood and bone marrow were sampled before and during the pollen season. TLR2 and TLR4 expression was determined flow cytometrically. Changes in the TLR receptor expression pattern were evaluated by a nasal challenge with allergen followed by LPS, or vice versa. Symptoms along with cells and cytokines in NAL were analyzed. Results: TLR4 expression increased in leukocytes in NAL, peripheral blood and bone marrow during symptomatic allergic rhinitis. A similar increase was seen for TLR2 in neutrophils in blood. Nasal challenge with allergen followed by LPS augmented the release of IL-4, IL-5, IL-10, IL-13, IFN-gamma and TNF-alpha. Conclusion: A systemic up-regulation of TLR4 in symptomatic allergic rhinitis may explain why LPS preceded by allergen increases nasal cytokine release. Copyright (C) 2012 S. Karger AG, Basel
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  • Hedenstierna, M, et al. (författare)
  • Long-term follow-up of successful hepatitis C virus therapy : waning immune responses and disappearance of liver disease are consistent with cure.
  • 2015
  • Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 41:6, s. 532-543
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A sustained viral response (SVR) after interferon-based therapy of chronic hepatitis C virus (HCV) infection is regarded to represent a cure. Previous studies have used different markers to clarify whether an SVR truly represents a cure, but no study has combined a clinical work-up with highly sensitive HCV RNA detection, and the determination of immune responses.AIM: To determine clinical, histological, virological and immunological markers 5-20 years after SVR.METHODS: In 54 patients, liver biochemistry, histology and elastography were evaluated. Liver biopsies, plasma and peripheral blood mononuclear cells (PBMCs) were tested for minute amounts of HCV RNA. HCV-specific T-cell responses were monitored by ELISpot and pentamer staining, and humoral responses by measuring HCV nonstructural (NS)3-specific antibodies and virus neutralisation.RESULTS: Liver disease regressed significantly in all patients, and 51 were HCV RNA-negative in all tissues tested. There was an inverse association between liver disease, HCV-specific T-cell responses and HCV antibody levels with time from SVR, supporting that the virus had been cleared. The three patients, who all lacked signs of liver disease, had HCV RNA in PBMCs 5-9 years after SVR. All three had HCV-specific T cells and NS3 antibodies, but no cross-neutralising antibodies.CONCLUSIONS: Our combined data confirm that a SVR corresponds to a long-term clinical cure. The waning immune responses support the disappearance of the antigenic stimulus. Transient HCV RNA traces may be detected in some patients up to 9 years after SVR, but no marker associates this with an increased risk for liver disease.
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