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  • 1
    In: Mechanisms of Ageing and Development, Elsevier BV, Vol. 126, No. 11 ( 2005-11), p. 1223-1229
    Type of Medium: Online Resource
    ISSN: 0047-6374
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2005
    detail.hit.zdb_id: 1502520-2
    SSG: 12
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  • 2
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 195, No. 12 ( 2007-06-15), p. 1779-1788
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    URL: Issue
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2007
    detail.hit.zdb_id: 1473843-0
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  • 3
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2011
    In:  The Journal of Immunology Vol. 186, No. 2 ( 2011-01-15), p. 924-930
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 186, No. 2 ( 2011-01-15), p. 924-930
    Abstract: Systemic lupus erythematosus is a chronic autoimmune disease characterized by loss of tolerance to self-Ags and activation of autoreactive T cells. Regulatory T (Treg) cells play a critical role in controlling the activation of autoreactive T cells. In this study, we investigated mechanisms of potential Treg cell defects in systemic lupus erythematosus using MRL-Faslpr/lpr (MRL/lpr) and MRL-Fas+/+ mouse models. We found a significant increase in CD4+CD25+Foxp3+ Treg cells, albeit with an altered phenotype (CD62L−CD69+) and with a reduced suppressive capacity, in the lymphoid organs of MRL strains compared with non-autoimmune C3H/HeOuj mice. A search for mechanisms underlying the altered Treg cell phenotype in MRL/lpr mice led us to find a profound reduction in Dicer expression and an altered microRNA (miRNA, miR) profile in MRL/lpr Treg cells. Despite having a reduced level of Dicer, MRL/lpr Treg cells exhibited a significant overexpression of several miRNAs, including let-7a, let-7f, miR-16, miR-23a, miR-23b, miR-27a, and miR-155. Using computational approaches, we identified one of the upregulated miRNAs, miR-155, that can target CD62L and may thus confer the altered Treg cell phenotype in MRL/lpr mice. In fact, the induced overexpression of miR-155 in otherwise normal (C3H/HeOuj) Treg cells reduced their CD62L expression, which mimics the altered Treg cell phenotype in MRL/lpr mice. These data suggest a role of Dicer and miR-155 in regulating Treg cell phenotype. Furthermore, simultaneous appearance of Dicer insufficiency and miR-155 overexpression in diseased mice suggests a Dicer-independent alternative mechanism of miRNA regulation under inflammatory conditions.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2011
    detail.hit.zdb_id: 1475085-5
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  • 4
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    Online Resource
    The American Association of Immunologists ; 2012
    In:  The Journal of Immunology Vol. 188, No. 1_Supplement ( 2012-05-01), p. 48.6-48.6
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 188, No. 1_Supplement ( 2012-05-01), p. 48.6-48.6
    Abstract: CLEC12A is a member of the C-type lectin receptor family with a cytoplasmic immunoreceptor tyrosine-based inhibitory motif. Murine CLEC12A is expressed on variety of cell types including dendritic cells, monocytes/macrophages, B cells, neutrophils and basophils but not NK cells. In humans, CLEC12A is reported to be expressed on dendritic cells (DC, both myeloid and plasmacytoid), monocytes, B cells (normal and leukemic) and NK cells, but not on T cells or basophils. Performing flow cytometric analysis of human peripheral blood leukocytes using an anti-human CLEC12A antibody (clone 50C1), we report CLEC12A expression on a subset of CD3, CD19 and CD56 negative cells. Further analysis revealed these cells to be CCR3+ basophils. Antibody mediated ligation of CLEC12A on DCs results in cytokine production and cellular maturation and can inhibit NK cell mediated cytotoxicity. In response to IgE and IL-3, basophils can induce Th2 differentiation and amphiregulin production, respectively. We hypothesize that ligation with CLEC12A will alter IL-3 and/or IgE mediated basophil activation, which will be studied in our ongoing work.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2012
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  • 5
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2019
    In:  The Journal of Immunology Vol. 202, No. 1_Supplement ( 2019-05-01), p. 52.20-52.20
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 202, No. 1_Supplement ( 2019-05-01), p. 52.20-52.20
    Abstract: Human CD115, also known as CSF-1R, is highly expressed by monocytes, macrophages, and dendritic cells. Here we show that detection of human CD115 on peripheral blood monocytes is dependent on both the anticoagulant and the storage time before sample processing. Commercially available CD115 antibody, clone 9-4D2-1E4, shows bright staining on blood samples collected in EDTA and citrate based anticoagulants and a dimmer staining intensity in blood collected in heparin. Clone 9-4D2-1E4 is not compatible with Cyto-Chex™ tubes. Consistent with published reports in mice, human CD115 signal is reduced within hours of collection. CD115 expression is further reduced after overnight storage at ambient temperature and is completely lost two days post collection. Reduced CD115 expression over time is most noticeable in whole blood collected in heparin. These results demonstrate that anti-coagulant and storage time are important considerations for current research projects and clinical trials targeting CD115 (CSF-1R).
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2019
    detail.hit.zdb_id: 1475085-5
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  • 6
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 176, No. 3 ( 2006-02-01), p. 1465-1473
    Abstract: Mouse and human CD4 T cells primed during an immune response may differentiate into effector phenotypes such as Th1 (secreting IFN-γ) or Th2 (secreting IL-4) that mediate effective immunity against different classes of pathogen. However, primed CD4 T cells can also remain uncommitted, secreting IL-2 and chemokines, but not IFN-γ or IL-4. We now show that human CD4 T cells primed by protein vaccines mostly secreted IL-2, but not IFN-γ, whereas in the same individuals most CD4 T cells initially primed by infection with live pathogens secreted IFN-γ. We further demonstrate that many tetanus-specific IL-2+IFN-γ− cells are uncommitted and that a single IL-2+IFN-γ− cell can differentiate into Th1 or Th2 phenotypes following in vitro stimulation under appropriate polarizing conditions. In contrast, influenza-specific IL-2+IFN-γ− CD4 cells maintained a Th1-like phenotype even under Th2-polarizing conditions. Similarly, adoptively transferred OTII transgenic mouse T cells secreted mainly IL-2 after priming with OVA in alum, but were biased toward IFN-γ secretion when primed with the same OVA peptide presented as a pathogen Ag during live infection. Thus, protein subunit vaccines may prime a unique subset of differentiated, but uncommitted CD4 T cells that lack some of the functional properties of committed effectors induced by infection. This has implications for the design of more effective vaccines against pathogens requiring strong CD4 effector T cell responses.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2006
    detail.hit.zdb_id: 1475085-5
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  • 7
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 176, No. 4 ( 2006-02-15), p. 2662-2668
    Abstract: CD8+ T cells in HIV-infected patients are believed to contribute to the containment of the virus and the delay of disease progression. However, the frequencies of HIV-specific CD8+ T cells, as measured by IFN-γ secretion and tetramer binding, often do not correlate with a delay in disease progression during chronic infection. Using the Lysispot and ELISPOT assays, we measured the frequencies of cytotoxic and IFN-γ-secreting T cells responding to overlapping peptides from Gag, Nef, Env, and Pol consensus HIV-1 clade B sequences. PBMC from the majority of HIV-infected subjects have significant frequencies of HIV-specific cells that killed targets within 5 h directly ex vivo. The relative frequencies of IFN-γ-secreting and cytotoxic cells varied markedly between different HIV peptide pools within the same patient, and some T cells lysed targets without secreting IFN-γ. These results indicate that measurement of IFN-γ production alone may be insufficient to evaluate the breadth of the HIV-specific T cell response. Also, neither the CTL to IFN-γ ratios nor the ex vivo CTL frequencies specific for different HIV proteins were consistently lower than responses specific for two other chronic viral infections, human CMV and EBV, within the same subjects. Thus ex vivo cytotoxic T cell frequencies do not provide evidence for a model of “preterminal differentiation” of HIV-specific CD8+ T cells during chronic HIV infection. Analysis of the frequency of directly cytotoxic HIV-specific T cells may be of considerable value in the assessment of disease progression and the potential efficacy of HIV vaccines.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2006
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  • 8
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2019
    In:  The Journal of Immunology Vol. 202, No. 1_Supplement ( 2019-05-01), p. 64.15-64.15
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 202, No. 1_Supplement ( 2019-05-01), p. 64.15-64.15
    Abstract: Human TLR9 (CD289) is a well characterized mediator of antiviral immunity. TLR9 is primarily activated by unmethylated CpG sequences leading to the production of type I interferons and other inflammatory cytokines. Recently, changes in TLR9 expression in cancer have also been reported. Here we describe novel monocloncal antibodies for the detection of human TLR9 by flow cytometry. These clones recognize intracellular TLR9 in B cells and plasmacytoid dendritic cells (pDCs), as well as on HEK293 cells transfected with human TLR9, and are compatible with multiple fixation and permeabilization buffers. We also show surface expression of TLR9 on pDCs, which is reported to be upregulated following stimulation. In response to CpG-B stimulation, two clones enhance and inhibit TLR9 signaling in a concentration dependent manner leading to alterations in cytokine secretion. Reported here are multiple human TLR9 clones with greater specificity than other commercially available clones.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2019
    detail.hit.zdb_id: 1475085-5
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  • 9
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2023
    In:  The Journal of Immunology Vol. 210, No. 1_Supplement ( 2023-05-01), p. 79.16-79.16
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 210, No. 1_Supplement ( 2023-05-01), p. 79.16-79.16
    Abstract: CD157 is an ectoenzyme that has both cyclic ADP-ribose hydrolase and ADP-ribosyl cyclase activities. In the human hematopoietic system, CD157 is prevalently expressed by cells of the myelomonocytic lineage, and interacts with extracellular matrix components and regulates leukocyte diapedesis via integrin-mediated signaling. CD157 is implicated in the pathophysiology of several neurological disorders. Although it lacks a cytoplasmatic domain, CD157 is able to transduce intracellular signals by establishing functional and structural crosstalk with β1 (CD29) and β2 (CD18) integrins. CD157 ligation causes integrin– dependent cytoskeletal remodeling and increase in F-actin content. Activation of downstream signaling pathways leads to cell polarization, with CD157 migrating prevalently to the rear of the cells whereas F-actin is localized at the opposite pole. However, the molecular and cellular functions of CD157 still remain poorly understood. Here, we describe the generation of a monoclonal antibody specific for human CD157 (clone W21007F) that can be used in flow cytometry, immunofluorescence and blocking of CD157 mediated adhesion of monocytes to fibronectin. Treatment of the pro-monocytic, myeloid leukemia cell line U937 with clone W21007F induces cell polarization and a marked increase in filamentous actin, with CD157 clustering at the uropod. The majority of F-Actin fibers are located at the opposite end of CD157, and CD157 co-localizes with integrin beta-1 in distinct membrane domains. The reference clone SY/11B5 and isotype control antibody do not show this effect. In conclusion, anti-human CD157 (clone W21007F) is a valuable tool for the study of CD157 function and expression in human cells.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2023
    detail.hit.zdb_id: 1475085-5
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  • 10
    Online Resource
    Online Resource
    Rockefeller University Press ; 2008
    In:  The Journal of Experimental Medicine Vol. 205, No. 5 ( 2008-05-12), p. 1099-1108
    In: The Journal of Experimental Medicine, Rockefeller University Press, Vol. 205, No. 5 ( 2008-05-12), p. 1099-1108
    Abstract: Most autoimmune diseases are more common in women than in men. This may be caused by differences in sex hormones, sex chromosomes, or both. In this study, we determined if there was a contribution of sex chromosomes to sex differences in susceptibility to two immunologically distinct disease models, experimental autoimmune encephalomyelitis (EAE) and pristane-induced lupus. Transgenic SJL mice were created to permit a comparison between XX and XY within a common gonadal type. Mice of the XX sex chromosome complement, as compared with XY, demonstrated greater susceptibility to both EAE and lupus. This is the first evidence that the XX sex chromosome complement, as compared with XY, confers greater susceptibility to autoimmune disease.
    Type of Medium: Online Resource
    ISSN: 1540-9538 , 0022-1007
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    Language: English
    Publisher: Rockefeller University Press
    Publication Date: 2008
    detail.hit.zdb_id: 1477240-1
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