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  • 1
    Online Resource
    Online Resource
    Wiley ; 2006
    In:  European Journal of Immunology Vol. 36, No. 6 ( 2006-06), p. 1583-1597
    In: European Journal of Immunology, Wiley, Vol. 36, No. 6 ( 2006-06), p. 1583-1597
    Type of Medium: Online Resource
    ISSN: 0014-2980 , 1521-4141
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2006
    detail.hit.zdb_id: 1491907-2
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  • 2
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2001
    In:  Proceedings of the National Academy of Sciences Vol. 98, No. 19 ( 2001-09-11), p. 10805-10810
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 19 ( 2001-09-11), p. 10805-10810
    Abstract: Flow cytometry was used to study signaling events in individual CD4 T cells after antigen recognition in the body. Phosphorylation of c-jun and p38 mitogen-activated protein kinase was detected within minutes in all antigen-specific CD4 T cells in secondary lymphoid tissues after injection of peptide antigen into the bloodstream. The remarkable rapidity of this response correlated with the finding that most naive T cells are in constant contact with dendritic antigen-presenting cells. Contrary to predictions from in vitro experiments, antigen-induced c-jun and p38 mitogen-activated protein kinase phosphorylation did not depend on CD28 signals and was insensitive to inhibition by cyclosporin A. Our results highlight the efficiency of the in vivo immune response and underscore the need to verify which signaling pathways identified in vitro actually operate under physiological conditions.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2001
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 3
    In: Cell Reports, Elsevier BV, Vol. 42, No. 1 ( 2023-01), p. 112014-
    Type of Medium: Online Resource
    ISSN: 2211-1247
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2649101-1
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  • 4
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2002
    In:  The Journal of Immunology Vol. 169, No. 12 ( 2002-12-15), p. 6659-6663
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 169, No. 12 ( 2002-12-15), p. 6659-6663
    Abstract: The role of B7/CD28 signals in Ag-induced cell cycle progression of CD4+ T cells was examined using the technique of CFSE dye dilution and flow cytometry. In wild-type T cells, proliferation was directly related to the concentration of Ag available to the APC. Consistent with this, the rate of G0→G1 cell cycle progression varied with the concentration of Ag. However, cell division by T cell blasts occurred at a constant rate, independent of Ag concentration. G0→G1 phase progression by CD28-deficient CD4+ T cells or wild-type T cells cultured in the presence of neutralizing anti-B7 mAbs was slowed, confirming that a synergy does exist between TCR and CD28 signaling in the initial activation of the T cells. However, unlike the TCR, the strength of CD28 stimulation was also shown to play a unique role in controlling the rate of cell division by T cell blasts.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2002
    detail.hit.zdb_id: 1475085-5
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  • 5
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2001
    In:  The Journal of Immunology Vol. 167, No. 2 ( 2001-07-15), p. 827-835
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 167, No. 2 ( 2001-07-15), p. 827-835
    Abstract: Untransformed CD4+ Th1 cells stimulated with Ag and APC demonstrated a dependence on B7- and CD28-mediated costimulatory signals for the expression and function of AP-1 proteins. The induction of transactivation by the c-fos gene regulator Elk-1 mirrored this requirement for TCR and CD28 signal integration. c-Jun N-terminal kinase (JNK) (but not extracellular signal-regulated kinase or p38) protein kinase activity was similarly inhibited by neutralizing anti-B7 mAbs. Blockade of JNK protein kinase activity with SB 202190 prevented both Elk-1 transactivation and c-Fos induction. These results identify a unique role for B7 costimulatory molecules and CD28 in the activation of JNK during Ag stimulation in Th1 cells, and suggest that JNK regulates Elk-1 transactivation at the c-fos gene to promote the formation of AP-1 complexes important to IL-2 gene expression.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2001
    detail.hit.zdb_id: 1475085-5
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  • 6
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2020
    In:  The Journal of Immunology Vol. 204, No. 1_Supplement ( 2020-05-01), p. 149.14-149.14
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 1_Supplement ( 2020-05-01), p. 149.14-149.14
    Abstract: Macrophages are key mediators of tissue homeostasis and inflammation and do so by virtue of differential expression of secreted and cell surface proteins. Cytokines such as IFNγ or IL-4 and IL-13 are known to generate classical proinflammatory M1 and alternatively activated M2 macrophages, respectively, but it is less clear how cell density, cell-cell contact and corticosteroids work together to affect macrophage function. Corticosteroids such as cortisol are known to downregulate the inflammatory signaling but they can also alter the expression of cell surface proteins, such as CD163, on steady-state macrophages. Here we examined the effect of monocyte seeding density and cortisol on the expression of cell surface proteins on human macrophages. The expression of the macrophage markers CD16, CD163, CD204 and VSIG4 were found to correlate with monocyte seeding density such that at low seeding densities, monocyte-derived macrophages were found to express minimal amounts of CD16, CD163, CD204 and VSIG4 while at high seeding densities, expression of these markers was restored. When cultured in the presence of cortisol, macrophages seeded at low densities were found to upregulate expression of these markers, but not CD204, to levels comparable to macrophages seeded at high densities grown in the presence of MCSF. Additionally, in the presence of cortisol, macrophages expressed higher levels of GPBAR1 which has also been shown to reduce classical proinflammatory macrophage activation in colitis models. This data suggests that corticosteroids may regulate macrophage function by modulating the expression of cell surface proteins such as GPBAR1 and not just interfering with morer conventional inflammatory cell signaling pathways..
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2020
    detail.hit.zdb_id: 1475085-5
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  • 7
    Online Resource
    Online Resource
    The American Association of Immunologists ; 1998
    In:  The Journal of Immunology Vol. 161, No. 8 ( 1998-10-15), p. 3896-3901
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 161, No. 8 ( 1998-10-15), p. 3896-3901
    Abstract: Fetal thymic organ culture of TCR transgenic (Tg) tissue has been used to study issues of timing and specificity in T cell development. Because most TCR Tgs express a rearranged αβ TCR on the cell surface at an earlier stage in development than normal mice, there is a possibility that the conclusions of studies using TCR Tg cultures may not apply to normal development. In particular, in our studies of peptide-induced development of CD8 T cells, it is possible that the peptide acts on the immature double-negative cell, driving development of CD8 T cells without passing through a double-positive stage. This issue was examined by asking whether MHC class I restriction was required and by analyzing CD8β levels and endogenous TCRα chain rearrangements. We found that if nonstimulatory peptides were used in fetal thymic organ culture, CD8 T cells developed via the conventional pathway, transiting through a double-positive stage. However, we could not rule out that cells selected in the presence of stimulatory peptides (agonists) did not develop directly from double-negative precursors.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 1998
    detail.hit.zdb_id: 1475085-5
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  • 8
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2018
    In:  The Journal of Immunology Vol. 200, No. 1_Supplement ( 2018-05-01), p. 46.16-46.16
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 200, No. 1_Supplement ( 2018-05-01), p. 46.16-46.16
    Abstract: Mesenchymal stem cells (MSCs) are multipotent adult stem cells found in a variety of tissues, including bone marrow, adipose, and umbilical cord. Although MSCs have the ability to differentiate into a variety of cell types useful for regenerative medicine, their ability to modulate the immune system has been at the forefront in the clinic. The mechanisms by which MSCs affect the immune system are not fully understood. This makes it difficult to design specific quality control measures for MSCs used for cell therapy as well as to understand what parameters are the most critical for their immunomodulatory abilities. This specific testing is important to determine batch-to-batch variability and to better forecast patient-to-patient efficacy. In this study, we demonstrate a workflow to investigate the effects of MSCs on immune cell subset populations. Human MSCs were co-cultured with human T cell subtypes (Th1, Th2, Th17, and Treg) that have been differentiated utilizing CellXVivo™ Differentiation Kits. Co-culture supernates are then analyzed via Proteome Profiler™ Antibody Arrays to screen for changes in cytokine levels, relative to MSCs cultured in the absence of T-cells. Analytes discovered to change in the screening arrays are then quantitated using Luminex® Assays. We hypothesize that these tools and techniques will allow for a better understanding of the mechanisms contributing to MSC immunomodulation and provide methods for routine quality control testing of MSC populations prior to clinical use.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2018
    detail.hit.zdb_id: 1475085-5
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  • 9
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 198, No. 1_Supplement ( 2017-05-01), p. 138.7-138.7
    Abstract: Macrophages are ubiquitously distributed throughout the various tissues of the body and perform many functions. These include inflammatory responses against pathogens by classically activated M1 macrophages and the regulation of wound healing and tissue remodeling by anti-inflammatory alternatively activated M2 macrophages. The responsibility for these pleiotropic functions lies in the expression of a myriad of surface receptors unique to a given subset. Much of what we know about the function of human macrophage subsets has been gleaned by studying in vitro generated macrophages, matured in the presence of GM-CSF or M-CSF, and polarized with different cytokines. Oftentimes, culture conditions (such as the type of serum used, the duration of the culture and the use of polarizing cytokines) vary between studies making direct comparisons difficult. Furthermore, overlap in surface marker expression can make it difficult to distinguish between the different macrophage subsets. We directly compared the expression of fifty different surface markers on M1 and M2a macrophages cultured in the presence of fetal bovine serum, human AB serum or serum free media and found that the type or presence of serum used affected the expression of several markers such as CD200R1 and CD32. Moreover, we compared the expression of these surface markers on polarized and unpolarized macrophages and determined that polarization was critical to the expression of several of these markers, such as CD38 and SLAM F7. The results of these studies should significantly expand our knowledge of the phenotypic differences between human M1 and M2a macrophages as well as demonstrate the importance of culture conditions in generating these phenotypes.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2017
    detail.hit.zdb_id: 1475085-5
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  • 10
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2009
    In:  The Journal of Immunology Vol. 182, No. 1_Supplement ( 2009-04-01), p. 96.14-96.14
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 182, No. 1_Supplement ( 2009-04-01), p. 96.14-96.14
    Abstract: Although IL-17A is made by CD4+ TH17 cells and there is an ever-increasing body of literature on these cells, other cells make IL-17A, including CD8+ (Tc17) and gamma-delta T cells, NK cells, and neutrophils. There are many factors that contribute to published findings of the percentage of cells producing IL-17A, including the activation or differentiation conditions, time course of activation, and antibody used for detection. It has been published that high levels of IL-17A are secreted by human PBMCs after anti-CD3/CD28-treatment alone for only 24 hrs. We have developed a new monoclonal Ab (clone 41802) that is specific for human IL-17A. The specificity of this Ab has been rigorously tested. Clone 41802 detects an increase in IL-17A in PMA/ionomycin-treated human PBMCs over resting cells by intracellular flow cytometry. This finding correlated with real-time PCR data in activated vs resting CD4+ PBMCs. This clone also detects IL-17A in a population of activated CD3+ PBMCs that is also positive for IL-22 and IL-23R by flow cytometry. Importantly, clone 41802 detects IL-17A in transfectant cells overexpressing human IL-17A, but not in cells overexpressing human IL-17F. The specificity of clone 41802 was further confirmed by western blot. In conclusion, clone 41802 is specific for human IL-17A. Although a larger percentage of IL-17A+ cells are detected in activated PBMCs than with other commercially available clones, this indicates an interesting biological finding, not a lack of antibody specificity.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2009
    detail.hit.zdb_id: 1475085-5
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