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  • 1
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    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2000-08-26
    Beschreibung: Whereas T helper cells recognize peptide-major histocompatibility complex (MHC) class II complexes through their T cell receptors (TCRs), CD4 binds to an antigen-independent region of the MHC. Using green fluorescent protein-tagged chimeras and three-dimensional video microscopy, we show that CD4 and TCR-associated CD3zeta cluster in the interface coincident with increases in intracellular calcium. Signaling-, costimulation-, and cytoskeleton-dependent processes then stabilize CD3zeta in a single cluster at the center of the interface, while CD4 moves to the periphery. Thus, the CD4 coreceptor may serve primarily to "boost" recognition of ligand by the TCR and may not be required once activation has been initiated.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krummel, M F -- Sjaastad, M D -- Wulfing, C -- Davis, M M -- New York, N.Y. -- Science. 2000 Aug 25;289(5483):1349-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Stanford University School of Medicine, and the Howard Hughes Medical Institute, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10958781" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Antigen-Presenting Cells/immunology ; Antigens, CD3/*metabolism ; Antigens, CD4/*metabolism ; Calcium Signaling ; Cell Line ; Cytoskeleton/physiology ; Histocompatibility Antigens Class II/immunology/metabolism ; Ligands ; *Lymphocyte Activation ; Microscopy, Video ; Phosphorylation ; Receptors, Antigen, T-Cell/immunology/metabolism ; Recombinant Fusion Proteins/metabolism ; T-Lymphocytes, Helper-Inducer/*immunology/metabolism ; Transfection
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Publikationsdatum: 2008-08-09
    Beschreibung: The prevention of autoimmunity requires the elimination of self-reactive T cells during their development and maturation. The expression of diverse self-antigens by stromal cells in the thymus is essential to this process and depends, in part, on the activity of the autoimmune regulator (Aire) gene. Here we report the identification of extrathymic Aire-expressing cells (eTACs) resident within the secondary lymphoid organs. These stromally derived eTACs express a diverse array of distinct self-antigens and are capable of interacting with and deleting naive autoreactive T cells. Using two-photon microscopy, we observed stable antigen-specific interactions between eTACs and autoreactive T cells. We propose that such a secondary network of self-antigen-expressing stromal cells may help reinforce immune tolerance by preventing the maturation of autoreactive T cells that escape thymic negative selection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532844/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532844/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gardner, James M -- Devoss, Jason J -- Friedman, Rachel S -- Wong, David J -- Tan, Ying X -- Zhou, Xuyu -- Johannes, Kellsey P -- Su, Maureen A -- Chang, Howard Y -- Krummel, Matthew F -- Anderson, Mark S -- K08 AI076429/AI/NIAID NIH HHS/ -- K08 AI076429-05/AI/NIAID NIH HHS/ -- P01 AI035297/AI/NIAID NIH HHS/ -- P01 AI035297-150009/AI/NIAID NIH HHS/ -- P01 AI035297-159001/AI/NIAID NIH HHS/ -- P01 AI035297-160009/AI/NIAID NIH HHS/ -- P01 AI035297-169001/AI/NIAID NIH HHS/ -- P01 AI035297-170009/AI/NIAID NIH HHS/ -- P01 AI035297-179001/AI/NIAID NIH HHS/ -- P30 DK063720/DK/NIDDK NIH HHS/ -- P30 DK063720-05/DK/NIDDK NIH HHS/ -- T32 GM007618/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Aug 8;321(5890):843-7. doi: 10.1126/science.1159407.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Diabetes Center, University of California San Francisco (UCSF), San Francisco, CA 94122, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18687966" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adoptive Transfer ; Animals ; Antigen Presentation ; Autoantigens/genetics/*immunology ; Autoimmunity ; Cell Proliferation ; Epithelial Cells/immunology ; Gene Expression Regulation ; Glucose-6-Phosphatase/immunology ; Lymph Nodes/cytology/*immunology/metabolism ; Lymphoid Tissue/*cytology/immunology/*metabolism ; Mice ; Mice, Transgenic ; Proteins/immunology ; *Self Tolerance ; Spleen/cytology/immunology/metabolism ; Stromal Cells/immunology/metabolism ; T-Lymphocytes/*immunology ; Thymus Gland/cytology/immunology ; Transcription Factors/genetics/*metabolism ; Transcription, Genetic
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Publikationsdatum: 2013-09-17
    Beschreibung: Eosinophils are specialized myeloid cells associated with allergy and helminth infections. Blood eosinophils demonstrate circadian cycling, as described over 80 years ago, and are abundant in the healthy gastrointestinal tract. Although a cytokine, interleukin (IL)-5, and chemokines such as eotaxins mediate eosinophil development and survival, and tissue recruitment, respectively, the processes underlying the basal regulation of these signals remain unknown. Here we show that serum IL-5 levels are maintained by long-lived type 2 innate lymphoid cells (ILC2) resident in peripheral tissues. ILC2 cells secrete IL-5 constitutively and are induced to co-express IL-13 during type 2 inflammation, resulting in localized eotaxin production and eosinophil accumulation. In the small intestine where eosinophils and eotaxin are constitutive, ILC2 cells co-express IL-5 and IL-13; this co-expression is enhanced after caloric intake. The circadian synchronizer vasoactive intestinal peptide also stimulates ILC2 cells through the VPAC2 receptor to release IL-5, linking eosinophil levels with metabolic cycling. Tissue ILC2 cells regulate basal eosinophilopoiesis and tissue eosinophil accumulation through constitutive and stimulated cytokine expression, and this dissociated regulation can be tuned by nutrient intake and central circadian rhythms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795960/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795960/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nussbaum, Jesse C -- Van Dyken, Steven J -- von Moltke, Jakob -- Cheng, Laurence E -- Mohapatra, Alexander -- Molofsky, Ari B -- Thornton, Emily E -- Krummel, Matthew F -- Chawla, Ajay -- Liang, Hong-Erh -- Locksley, Richard M -- AI007334/AI/NIAID NIH HHS/ -- AI007641/AI/NIAID NIH HHS/ -- AI026918/AI/NIAID NIH HHS/ -- AI030663/AI/NIAID NIH HHS/ -- AI078869/AI/NIAID NIH HHS/ -- DK063720/DK/NIDDK NIH HHS/ -- DP1 AR064158/AR/NIAMS NIH HHS/ -- HL107202/HL/NHLBI NIH HHS/ -- P01 HL024136/HL/NHLBI NIH HHS/ -- P01 HL107202/HL/NHLBI NIH HHS/ -- P30 DK063720/DK/NIDDK NIH HHS/ -- R01 AI030663/AI/NIAID NIH HHS/ -- R37 AI026918/AI/NIAID NIH HHS/ -- T32 AI007641/AI/NIAID NIH HHS/ -- T32 GM007618/GM/NIGMS NIH HHS/ -- T32 HD044331/HD/NICHD NIH HHS/ -- U19 AI077439/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Oct 10;502(7470):245-8. doi: 10.1038/nature12526. Epub 2013 Sep 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of California San Francisco, San Francisco, California 94143-0795, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24037376" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Cells, Cultured ; Circadian Rhythm ; Collagen/metabolism ; Eosinophils/immunology/*metabolism/parasitology ; Female ; Gene Expression Regulation ; *Homeostasis ; Interleukin-13/genetics/metabolism ; Interleukin-5/blood/genetics/metabolism ; Lung/immunology/metabolism/parasitology ; Lymphocytes/immunology/*metabolism/parasitology ; Male ; Mice ; Mice, Inbred C57BL ; Nippostrongylus/physiology ; Strongylida Infections/immunology
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
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    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 1995-11-10
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Allison, J P -- Krummel, M F -- New York, N.Y. -- Science. 1995 Nov 10;270(5238):932-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7481795" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Abatacept ; Animals ; Antigens, CD ; Antigens, CD28/*immunology ; Antigens, CD80/immunology ; Antigens, Differentiation/*immunology ; CTLA-4 Antigen ; Down-Regulation ; Humans ; *Immunoconjugates ; *Lymphocyte Activation ; Mice ; Mice, Knockout ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes/*immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
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    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 1996-03-22
    Beschreibung: One reason for the poor immunogenicity of many tumors may be that they cannot provide signals for CD28-mediated costimulation necessary to fully activate T cells. It has recently become apparent that CTLA-4, a second counterreceptor for the B7 family of costimulatory molecules, is a negative regulator of T cell activation. Here, in vivo administration of antibodies to CTLA-4 resulted in the rejection of tumors, including preestablished tumors. Furthermore, this rejection resulted in immunity to a secondary exposure to tumor cells. These results suggest that blockade of the inhibitory effects of CTLA-4 can allow for, and potentiate, effective immune responses against tumor cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leach, D R -- Krummel, M F -- Allison, J P -- CA09179/CA/NCI NIH HHS/ -- CA40041/CA/NCI NIH HHS/ -- CA57986/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1996 Mar 22;271(5256):1734-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8596936" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Abatacept ; Animals ; Antibodies/immunology ; Antigens, CD ; Antigens, CD28/immunology ; Antigens, CD80/immunology ; Antigens, Differentiation/*immunology ; CTLA-4 Antigen ; Female ; Graft Rejection ; *Immunoconjugates ; Immunologic Memory ; *Lymphocyte Activation ; Mice ; Mice, Inbred A ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Neoplasms, Experimental/*immunology ; T-Lymphocytes/*immunology ; Transfection ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    Publikationsdatum: 2016-03-17
    Beschreibung: Lung metastasis is the lethal determinant in many cancers and a number of lines of evidence point to monocytes and macrophages having key roles in its development. Yet little is known about the immediate fate of incoming tumour cells as they colonize this tissue, and even less known about how they make first contact with the immune system. Primary tumours liberate circulating tumour cells (CTCs) into the blood and we have developed a stable intravital two-photon lung imaging model in mice for direct observation of the arrival of CTCs and subsequent host interaction. Here we show dynamic generation of tumour microparticles in shear flow in the capillaries within minutes of CTC entry. Rather than dispersing under flow, many of these microparticles remain attached to the lung vasculature or independently migrate along the inner walls of vessels. Using fluorescent lineage reporters and flow cytometry, we observed 'waves' of distinct myeloid cell subsets that load differentially and sequentially with this CTC-derived material. Many of these tumour-ingesting myeloid cells collectively accumulated in the lung interstitium along with the successful metastatic cells and, as previously understood, promote the development of successful metastases from surviving tumour cells. Although the numbers of these cells rise globally in the lung with metastatic exposure and ingesting myeloid cells undergo phenotypic changes associated with microparticle ingestion, a consistently sparse population of resident conventional dendritic cells, among the last cells to interact with CTCs, confer anti-metastatic protection. This work reveals that CTC fragmentation generates immune-interacting intermediates, and defines a competitive relationship between phagocyte populations for tumour loading during metastatic cell seeding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Headley, Mark B -- Bins, Adriaan -- Nip, Alyssa -- Roberts, Edward W -- Looney, Mark R -- Gerard, Audrey -- Krummel, Matthew F -- P01 HL024136/HL/NHLBI NIH HHS/ -- R21 CA167601/CA/NCI NIH HHS/ -- R21CA167601/CA/NCI NIH HHS/ -- U54 CA163123/CA/NCI NIH HHS/ -- England -- Nature. 2016 Mar 24;531(7595):513-7. doi: 10.1038/nature16985. Epub 2016 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of California, San Francisco, 513 Parnassus Ave, HSW512, San Francisco, California 94143-0511, USA. ; Department of Medical Oncology, Academic Medical Center Amsterdam, Meibergdreef, 91105AZ Amsterdam, The Netherlands. ; Departments of Medicine and Laboratory Medicine, University of California, San Francisco, 513 Parnassus Avenue, HSW512, California 94143-0511, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26982733" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Capillaries/pathology ; Cell Line, Tumor ; Cell Lineage ; *Cell Movement ; Dendritic Cells/cytology/immunology ; Female ; Genes, Reporter/genetics ; Humans ; Lung/blood supply/cytology/*immunology/*pathology ; Lung Neoplasms/*immunology/pathology/*secondary ; Male ; Melanoma, Experimental/immunology/pathology ; Mice ; Microscopy, Confocal ; Myeloid Cells/cytology ; Neoplasm Metastasis/*immunology/*pathology ; Neoplastic Cells, Circulating/pathology
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    Publikationsdatum: 2017-05-12
    Beschreibung: During immune surveillance, T cells survey the surface of antigen-presenting cells. In searching for peptide-loaded major histocompatibility complexes (pMHCs), they must solve a classic trade-off between speed and sensitivity. It has long been supposed that microvilli on T cells act as sensory organs to enable search, but their strategy has been unknown. We used lattice light-sheet and quantum dot–enabled synaptic contact mapping microscopy to show that anomalous diffusion and fractal organization of microvilli survey the majority of opposing surfaces within 1 minute. Individual dwell times were long enough to discriminate pMHC half-lives and T cell receptor (TCR) accumulation selectively stabilized microvilli. Stabilization was independent of tyrosine kinase signaling and the actin cytoskeleton, suggesting selection for avid TCR microclusters. This work defines the efficient cellular search process against which ligand detection takes place.
    Schlagwort(e): Cell Biology, Online Only
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Publikationsdatum: 2010-10-04
    Print ISSN: 0027-8424
    Digitale ISSN: 1091-6490
    Thema: Biologie , Medizin , Allgemeine Naturwissenschaft
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Publikationsdatum: 2014-06-10
    Print ISSN: 0027-8424
    Digitale ISSN: 1091-6490
    Thema: Biologie , Medizin , Allgemeine Naturwissenschaft
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Publikationsdatum: 2002-11-01
    Print ISSN: 0027-8424
    Digitale ISSN: 1091-6490
    Thema: Biologie , Medizin , Allgemeine Naturwissenschaft
    Standort Signatur Erwartet Verfügbarkeit
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