Search results for "Degranulation"
showing 10 items of 81 documents
Combining dasatinib with dexamethasone long-term leads to maintenance of antiviral and antileukemia specific cytotoxic T cell responses in vitro
2012
Maintaining graft versus leukemia (GvL) and antivirus responses of cytotoxic T cells (CTLs) while suppressing graft-versus-host disease (GvHD) remains a challenge after allogeneic bone marrow transplantation. Clinical observations indicate that combining glucocorticoids with multi-tyrosine-kinase inhibitors could be a successful therapeutic approach. We and others have shown that the BCR-ABL/SRC kinase inhibitor dasatinib may enhance or suppress T cells in vitro. In this report, we evaluated combination effects of dasatinib and dexamethasone on CD3 + and virus-specific CD8 + T cells directly ex vivo and on antigen-specific leukemia-reactive and alloreactive CD8 + T cell clones. Functional o…
An Ovalbumin Peptide-Specific Cytotoxic T Cell Clone with Antigen Self-Presentation Capacity Uses Two Distinct Mechanisms to Kill Target Cells
1993
Abstract Cloned 10BK.1 T cells with specificity for the ovalbumin peptide OVA257-264 are representative of a novel cell type within the CD8 + subset of T cells. In the presence and in the absence of added antigen presenting cells these T cells react toward antigen (Ag) by proliferation and lymphokine production. These data suggest self-presentation of the Ag by 10BK.1 cells. Here we present evidence that 10BK.1 cells exhibit cytotoxic activity that involves two different cytotoxic effector mechanisms. (i) One mechanism is fast killing activity, apparent within 4 hr. Constitutive mouse T cell-specific proteinase-1 (MTSP-1) activity, constitutive expression of MTSP-1 RNA, increased by Ag chal…
Mast cells promote homeostasis by limiting endothelin-1-induced toxicity
2004
Endothelin-1 (ET-1) is a 21-amino-acid peptide, derived from vascular endothelial cells, with potent vasoconstrictor activity. ET-1 has been implicated in diverse physiological or pathological processes, including the vascular changes associated with sepsis. However, the factors that regulate ET-1-associated toxicity during bacterial infections, or in other settings, are not fully understood. Both the pathology associated with certain allergic and autoimmune disorders, and optimal host defence against bacterial and parasitic infections are mediated by mast cells. In vitro, mast cells can produce ET-1 (ref. 11), undergo ET-1-dependent and endothelin-A receptor (ET(A))-dependent activation, a…
Inflammatory Murine Skin Responses to UV-B Light Are Partially Dependent on Endothelin-1 and Mast Cells
2006
Endothelin (ET-1) has been shown to crucially contribute to UV-induced skin responses such as tanning. To test whether ET-1 is also involved in early cutaneous reactions to UV, we assessed ET-1 skin levels in UV-irradiated mice. In correlation with the levels of UV-induced skin inflammation, ET-1 concentrations increased substantially and continually. Moreover, blocking of ET-1 receptors (ET A ) resulted in significantly decreased cutaneous inflammation following UV irradiation. When we assessed skin responses to ET-1 injections, we observed prominent mast cell degranulation and mast cell-dependent inflammation. Since mast cells also critically contributed to UV-induced inflammation, we det…
Encapsulation Response ofCiona intestinalis(Ascidiacea) to Intratunical Erythrocyte Injection
1997
Abstract Electron microscopic studies on the encapsulation induced by erythrocyte injection into the tunic of the ascidian Ciona intestinalis were carried out. The observations reported in the present paper complete the description previously given of capsule architecture and contribute to the characterization of the cells involved in the inflammatory reaction. The inflamed area is surrounded by an ample and peculiar “three-layered coat” respectively composed of flattened and packed extratunical hemocytes, the monolayered epithelium, and a layer of intratunical electron-dense particles. The latter are also clustered, variously arranged, and distributed in the tunic ground substance. The epi…
Specific and Redundant Roles for NFAT Transcription Factors in the Expression of Mast Cell-Derived Cytokines
2006
Abstract By virtue of their ability to express a plethora of biologically highly active mediators, mast cells (MC) are involved in both adaptive and innate immune responses. MC-derived Th2-type cytokines are thought to act as local amplifiers of Th2 reactions, including chronic inflammatory disorders such as allergic asthma, whereas MC-derived TNF-α is a critical initiator of antimicrobial defense. In this study, we demonstrate that the transcription factors NFATc1 and NFATc2 are part of a MC-specific signaling network that regulates the expression of TNF-α and IL-13, whereas NFATc3 is dispensable. Primary murine bone marrow-derived MC from NFATc2−/− mice, activated by either ionomycin or I…
Prevention of long-term IgE antibody production by gene gun-mediated DNA vaccination.
2004
Background Vaccination with allergen-encoding DNA represents a promising approach for the treatment of allergic diseases. Objective In a mouse model of type I allergy, we analyzed the ability of biolistic transfection to inhibit antigen-specific IgE production and to modulate T H 2 responses. Methods BALB/c mice were vaccinated by means of gene gun–mediated DNA immunization with plasmid vector pCMV-βGal, encoding β-galactosidase as a model allergen. Subsequently, mice were immunized by means of repeated intraperitoneal injection of β-galactosidase adsorbed to the adjuvant aluminum hydroxide. Development of IgE, IgG1, and IgG2a antibody titers during the course of immunization was followed, …
Mast cells are crucial for early inflammation, migration of Langerhans cells, and CTL responses following topical application of TLR7 ligand in mice.
2007
Abstract Until recently, IgE-activated mast cells have been regarded merely as effector cells of adaptive immune responses, involved in allergic reactions and mucosal immunity to parasites. Herein, we report that murine dermal mast cells, activated by local administration of a cream containing the synthetic TLR7 ligand imiquimod, are essential to initiate an early inflammatory reaction. The mast-cell–derived cytokines TNF-α and IL-1β play an important role in this process. Furthermore, TLR7-activated mast cells are also able to promote the emigration of Langerhans cells, which partly depends on the expression of mast-cell–derived IL-1β. We have previously shown that TLR7 ligation enhances t…
Classical and alternative pathways of mast cell activation.
2002
It has long since been recognized that mast cells are critical effectors of anaphylactic reactions, and the existence of these potentially hazardous cells has solely been justified due to their beneficial role in some infections with extracellular parasites. A novel understanding of mast cells as sentinels of the immune system has been made possible by taking advantage of mast cell-deficient mice in order to study the roles of mast cells in vivo and by detailed analyses of mast cell activation in vitro. Collectively, these experiments have revealed a variety of IgE-independent stimuli, which lead to the activation of mast cells as crucial initiators of an inflammatory response. Besides thei…
Interleukin-2 immediate type hypersensitivity?
2008
Two patients with metastatic malignant melanoma developed immediate type hypersensitivity-like symptoms while being treated with recombinant interleukin-(IL-)2 immunotherapy. Both patients showed positive skin prick tests to IL-2, enhanced basophil degranulation in vitro and responded to anti-histamines, but laboratory investigations suggested an IgE-independent, pseudoallergic mast cell degranulation against IL-2.