The Experts below are selected from a list of 3492 Experts worldwide ranked by ideXlab platform
David W. Hoskin - One of the best experts on this subject based on the ideXlab platform.
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cd2 CD48 interactions promote interleukin 2 and interferon γ synthesis by stabilizing cytokine mrna
Cellular Immunology, 2004Co-Authors: Bruce L. Musgrave, Carrie L. Watson, S. M. Mansour Haeryfar, Christine A. Barnes, David W. HoskinAbstract:CD2-CD48 interactions enhance T cell receptor-driven mouse T lymphocyte activation. However, the mechanism is not well understood. Here we show that blockade of CD2-CD48 interactions with anti-CD48 monoclonal antibody (mAb) inhibited interleukin (IL)-2 and interferon (IFN)-gamma expression, as well as T cell proliferation in response to mitogenic anti-CD3 mAb, although more potent inhibition resulted from blocking CD28-CD80/CD86 interactions. Blockade of both CD2 and CD28 costimulation abrogated T cell proliferation and cytokine synthesis. Conversely, T cells stimulated with immobilized anti-CD3 and anti-CD2 mAb exhibited increased proliferation and IL-2 and IFN-gamma expression, although a stronger enhancing effect was obtained with immobilized anti-CD3 and anti-CD28 mAb. Concurrent CD2 and CD28 costimulation caused a further increase in proliferation and cytokine synthesis. Stimulation of purified T cells with microsphere-immobilized anti-CD3 and anti-CD2 mAb increased IL-2 and IFN-gamma mRNA stability. However, CD28 costimulation had a stronger enhancing effect on IL-2 and IFN-gamma mRNA stability that was not further increased by concomitant CD2 signaling. CD2, therefore, costimulates T cell activation by stabilizing cytokine mRNA transcripts, albeit with less efficiency than CD28.
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CD2–CD48 interactions promote interleukin-2 and interferon-γ synthesis by stabilizing cytokine mRNA
Cellular immunology, 2004Co-Authors: Bruce L. Musgrave, Carrie L. Watson, S. M. Mansour Haeryfar, Christine A. Barnes, David W. HoskinAbstract:CD2-CD48 interactions enhance T cell receptor-driven mouse T lymphocyte activation. However, the mechanism is not well understood. Here we show that blockade of CD2-CD48 interactions with anti-CD48 monoclonal antibody (mAb) inhibited interleukin (IL)-2 and interferon (IFN)-gamma expression, as well as T cell proliferation in response to mitogenic anti-CD3 mAb, although more potent inhibition resulted from blocking CD28-CD80/CD86 interactions. Blockade of both CD2 and CD28 costimulation abrogated T cell proliferation and cytokine synthesis. Conversely, T cells stimulated with immobilized anti-CD3 and anti-CD2 mAb exhibited increased proliferation and IL-2 and IFN-gamma expression, although a stronger enhancing effect was obtained with immobilized anti-CD3 and anti-CD28 mAb. Concurrent CD2 and CD28 costimulation caused a further increase in proliferation and cytokine synthesis. Stimulation of purified T cells with microsphere-immobilized anti-CD3 and anti-CD2 mAb increased IL-2 and IFN-gamma mRNA stability. However, CD28 costimulation had a stronger enhancing effect on IL-2 and IFN-gamma mRNA stability that was not further increased by concomitant CD2 signaling. CD2, therefore, costimulates T cell activation by stabilizing cytokine mRNA transcripts, albeit with less efficiency than CD28.
Bruce L. Musgrave - One of the best experts on this subject based on the ideXlab platform.
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cd2 CD48 interactions promote interleukin 2 and interferon γ synthesis by stabilizing cytokine mrna
Cellular Immunology, 2004Co-Authors: Bruce L. Musgrave, Carrie L. Watson, S. M. Mansour Haeryfar, Christine A. Barnes, David W. HoskinAbstract:CD2-CD48 interactions enhance T cell receptor-driven mouse T lymphocyte activation. However, the mechanism is not well understood. Here we show that blockade of CD2-CD48 interactions with anti-CD48 monoclonal antibody (mAb) inhibited interleukin (IL)-2 and interferon (IFN)-gamma expression, as well as T cell proliferation in response to mitogenic anti-CD3 mAb, although more potent inhibition resulted from blocking CD28-CD80/CD86 interactions. Blockade of both CD2 and CD28 costimulation abrogated T cell proliferation and cytokine synthesis. Conversely, T cells stimulated with immobilized anti-CD3 and anti-CD2 mAb exhibited increased proliferation and IL-2 and IFN-gamma expression, although a stronger enhancing effect was obtained with immobilized anti-CD3 and anti-CD28 mAb. Concurrent CD2 and CD28 costimulation caused a further increase in proliferation and cytokine synthesis. Stimulation of purified T cells with microsphere-immobilized anti-CD3 and anti-CD2 mAb increased IL-2 and IFN-gamma mRNA stability. However, CD28 costimulation had a stronger enhancing effect on IL-2 and IFN-gamma mRNA stability that was not further increased by concomitant CD2 signaling. CD2, therefore, costimulates T cell activation by stabilizing cytokine mRNA transcripts, albeit with less efficiency than CD28.
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CD2–CD48 interactions promote interleukin-2 and interferon-γ synthesis by stabilizing cytokine mRNA
Cellular immunology, 2004Co-Authors: Bruce L. Musgrave, Carrie L. Watson, S. M. Mansour Haeryfar, Christine A. Barnes, David W. HoskinAbstract:CD2-CD48 interactions enhance T cell receptor-driven mouse T lymphocyte activation. However, the mechanism is not well understood. Here we show that blockade of CD2-CD48 interactions with anti-CD48 monoclonal antibody (mAb) inhibited interleukin (IL)-2 and interferon (IFN)-gamma expression, as well as T cell proliferation in response to mitogenic anti-CD3 mAb, although more potent inhibition resulted from blocking CD28-CD80/CD86 interactions. Blockade of both CD2 and CD28 costimulation abrogated T cell proliferation and cytokine synthesis. Conversely, T cells stimulated with immobilized anti-CD3 and anti-CD2 mAb exhibited increased proliferation and IL-2 and IFN-gamma expression, although a stronger enhancing effect was obtained with immobilized anti-CD3 and anti-CD28 mAb. Concurrent CD2 and CD28 costimulation caused a further increase in proliferation and cytokine synthesis. Stimulation of purified T cells with microsphere-immobilized anti-CD3 and anti-CD2 mAb increased IL-2 and IFN-gamma mRNA stability. However, CD28 costimulation had a stronger enhancing effect on IL-2 and IFN-gamma mRNA stability that was not further increased by concomitant CD2 signaling. CD2, therefore, costimulates T cell activation by stabilizing cytokine mRNA transcripts, albeit with less efficiency than CD28.
Arthur Weiss - One of the best experts on this subject based on the ideXlab platform.
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receptor like tyrosine phosphatases cd45 and cd148 have distinct functions in chemoattractant mediated neutrophil migration and response to s aureus
Immunity, 2011Co-Authors: Jing W Zhu, Kristin Doan, Jason S Park, Angela H Chau, Hong Zhang, Clifford A Lowell, Arthur WeissAbstract:Summary Neutrophils, critical innate immune effectors, use bacterial-derived chemoattractant-induced G protein-coupled receptor (GPCR) signaling for their pursuit of bacteria. Tyrosine phosphorylation pathways and receptor-like tyrosine phosphatases (RPTPs) are rarely considered in chemoattractant-mediated GPCR signaling. Here, we report that two RPTPs, CD45 and CD148, previously shown to share redundant roles in positively regulating Src family kinases (SFKs) in immunoreceptor signaling pathways in B cells and macrophages, are critical in the neutrophil response to S . aureus infection and, surprisingly, in chemoattractant-mediated chemotaxis. Remarkably, deficiency in either of these RPTPs influenced neutrophil GPCR responses in unique ways. Our results reveal that CD45 positively while CD148 positively and negatively regulate GPCR function and proximal signals including Ca 2+ , phosphatidylinositol 3′OH kinase (PI3K), and phospho-extracellular regulated kinase (pERK) activity. Moreover, our results suggest that CD45 and CD148 preferentially target different SFK members (Hck and Fgr versus Lyn, respectively) to positively and negatively regulate GPCR pathways.
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regulation of src family kinases involved in t cell receptor signaling by protein tyrosine phosphatase cd148
Journal of Biological Chemistry, 2011Co-Authors: Ondrej Stepanek, Arthur Weiss, Tomas Kalina, Peter Draber, Tereza Skopcova, Karel Svojgr, Pavla Angelisova, Vaclav Horejsi, Tomas BrdickaAbstract:CD148 is a receptor-like protein-tyrosine phosphatase known to inhibit transduction of mitogenic signals in non-hematopoietic cells. Similarly, in the hematopoietic lineage, CD148 inhibited signal transduction downstream of T cell receptor. However, it also augmented immunoreceptor signaling in B cells and macrophages via dephosphorylating C-terminal tyrosine of Src family kinases (SFK). Accordingly, endogenous CD148 compensated for the loss of the main SFK activator CD45 in murine B cells and macrophages but not in T cells. Hypothetical explanations for the difference between T cells and other leukocyte lineages include the inability of CD148 to dephosphorylate a specific set of SFKs involved in T cell activation or the lack of CD148 expression during critical stages of T cell development. Here we describe striking differences in CD148 expression between human and murine thymocyte subsets, the only unifying feature being the absence of CD148 during the positive selection when the major developmental block occurs under CD45 deficiency. Moreover, we demonstrate that similar to CD45, CD148 has both activating and inhibitory effects on the SFKs involved in TCR signaling. However, in the absence of CD45, activating effects prevail, resulting in functional complementation of CD45 deficiency in human T cell lines. Importantly, this is independent of the tyrosines in the CD148 C-terminal tail, contradicting the recently proposed phosphotyrosine displacement model as a mechanism of SFK activation by CD148. Collectively, our data suggest that differential effects of CD148 in T cells and other leukocyte subsets cannot be explained by the CD148 inability to activate T cell SFKs but rather by its dual inhibitory/activatory function and specific expression pattern.
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structurally distinct phosphatases cd45 and cd148 both regulate b cell and macrophage immunoreceptor signaling
Immunity, 2008Co-Authors: Jing W Zhu, Tomas Brdicka, Tamiko R Katsumoto, Joseph Lin, Arthur WeissAbstract:The receptor-type protein tyrosine phosphatase (RPTP) CD148 is thought to have an inhibitory function in signaling and proliferation in nonhematopoietic cells. However, its role in the immune system has not been thoroughly studied. Our analysis of CD148 loss-of-function mice showed that CD148 has a positive regulatory function in B cells and macrophages, similar to the role of CD45 as a positive regulator of Src family kinases (SFKs). Analysis of CD148 and CD45 doubly deficient B cells and macrophages revealed hyperphosphorylation of the C-terminal inhibitory tyrosine of SFKs accompanied by substantial alterations in B and myeloid lineage development and defective immunoreceptor signaling. Because these findings suggest the C-terminal tyrosine of SFKs is a common substrate for both CD148 and CD45 phosphatases and imply a level of redundancy not previously appreciated, a reassessment of the function of CD45 in the B and myeloid lineages based on prior data from the CD45-deficient mouse is warranted.
Ivan Stamenkovic - One of the best experts on this subject based on the ideXlab platform.
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distinct regulatory roles of lymphocyte costimulatory pathways on t helper type 2 mediated autoimmune disease
Journal of Experimental Medicine, 1996Co-Authors: Luigi Biancone, G Andres, H Ahn, Alice Lim, C Dai, R Noelle, H Yagita, C De Martino, Ivan StamenkovicAbstract:We assessed the role of CD40-CD40L, cytotoxic T lymphocyte (CTL)A4/CD28-B7s, and CD2-CD48/CD58 lymphocyte costimulatory pathways in the development of mercury chloride (HgCl2)-induced autoimmune disease in mice, which is believed to be mediated by T helper (Th) subset Th2. Inhibition of CD40-CD40-L and CTLA4/CD28-B7s interactions by anti-CD40-L antibody and soluble CTLA4-immunoglobulin (Ig) fusion protein, respectively, abrogated the autoimmune disease without affecting interleukin 4 (IL-4) production, showing the importance of physical contact between T and B lymphocytes in the Th2-mediated process. In contrast, two anti-CD2 antibodies that have been shown to induce immunosuppression of Th1-mediated events exacerbated the autoantibody response and augmented IgG1, IgE, and IL-4 production, transforming a mild mesangial glomerulopathy into a severe systemic immune complex disease. These observations demonstrate that manipulation of lymphocyte accessory counterreceptor interactions may affect the course of Th2-associated autoimmune disease and suggest that signals resulting from CD2 engagement play an essential role in the regulation of the Th1-Th2 effector equilibrium.
Yong Sung Choi - One of the best experts on this subject based on the ideXlab platform.
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CD48 Delivers an Accessory Signal for CD40-Mediated Activation of Human B Cells
Cellular immunology, 1996Co-Authors: Elena N. Klyushnenkova, Richard J. Armitage, Yong Sung ChoiAbstract:CD48, a glycosyl phosphatidylinositol anchored molecule has recently been shown to be a ligand for the T cell surface protein CD2 in mouse, human, and rat. It is expressed on practically all human T and B cells; however, its function remains unknown. We examined whether CD48 may be involved in the delivery of activating signals to human B cells. Costimulation with anti-CD48 J4-57 significantly increased CD40-mediated activation of tonsillar B cells. Costimulatory effect of anti-CD48 was observed on B cell aggregation, proliferation, and IgG secretion. Anti-CD48 alone did not stimulate resting B cells. Accessory signal provided through CD48 required the presence of IL-4 and/or IL-10, whereas responses of B cells to IL-2 was not affected. Ligation of CD48 by specific antibody induced CD23 expression on IL-4-stimulated Ramos B cell line but did not affect expression of CD25. We also examined the biochemical nature of the costimulatory effect of anti-CD40 and CD48. Ligation of CD40 or CD48 on the B cells induced tyrosine phosphorylation of proteins. CD40 induced earlier changes in the protein phosphorylation than CD48 did. Taken together, our data suggest that the stimulation via CD40 provides initial signals to activate B cells and CD48 may be involved in enhancing the activating signal to B cells, resulting in increased responsiveness of B cells to IL-4 and IL-10.
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stimulation of germinal center b lymphocyte proliferation by an fdc like cell line hk
Journal of Immunology, 1995Co-Authors: Xinhong Zhang, E Klyushnenkova, Yong Sung ChoiAbstract:To identify the signals given to the germinal center (GC) B cells by FDC, we have established an FDC-like cell line, HK. HK cells have the important functions of FDC, which are the preferential binding and stimulation of GC B cells. Cell-cell interaction between IgD- B cells and HK cells resulted in the rescue of these cells from apoptosis, whereas the majority of unbound B cells or B cells cultured in the absence of HK cells underwent apoptosis. We investigated the effects of HK cells on the subpopulations of tonsillar B lymphocytes that are at different stages of maturation and differentiation. The subpopulations of tonsillar B cells were purified by panning and/or MACS according to the surface expression of IgD, CD38, and CD44. Although HK cells alone did not stimulate B cell proliferation, HK cells in the presence of either anti-mu or anti-CD40 significantly enhanced the proliferation of B cells. The data show that HK cells preferentially bind, rescue, and stimulate GC B cells (IgD-CD38+) generating CD38-CD44+ memory B cells. The costimulation activity of HK cells is also provided in a form of soluble factor(s). Hence, the phenotypic and functional analysis of HK cells suggests that these cells may be derived from FDC.