Search results for "ACTIVATION"
showing 10 items of 2079 documents
Synthesis and expression of MHC class II molecules in the absence of attached invariant chains by recombinant-interferon-gamma-activated bone-marrow-…
1987
Pure populations of in vitro propagated bone marrow-derived macrophages are constitutively Ia negative. Co-culturing of these cells with recombinant interferon-gamma (rIFN-gamma) resulted in the appearance of high amounts of Ia antigens at the cell surface of essentially all cells. The continuous presence of the stimulus was a prerequisite for sustained Ia expression because removal of the stimulus resulted in rapid decline of surface Ia. Two-dimensional (2D) gel analysis (1D isoelectric focusing, 2D sodium dodecyl sulfate-polyacrylamide gel electrophoresis) of class II molecules synthesized by rIFN-gamma-stimulated bone marrow macrophages (BMM phi) revealed that, in contrast to class II co…
Quantitative studies of the secretion of complement component C3 by resident, elicited and activated macrophages. Comparison with C2, C4 and lysosoma…
1982
To quantitate the secretion of complement component C3 by guinea pig peritoneal macrophages an enzyme-linked immunosorbent assay was developed. C3 secretion was studied in resident, elicited and activated macrophages and compared with release of hemolytically active C2 and C4, as well as the lysosomal enzyme β-D-2-acetamido-2-deoxyglucosidase. Resident macrophages secreted about 6 ng C3/106 cells/h into culture supernatants over a period of 12 h. Corynebacterium parvum-activated cells were found to secrete 3 times that amount at nearly constant rates. There was a stepwise increase in secretion of functional C2 and C4 when comparing resident, elicited and activated macrophages; secretion was…
Modulation of C1q mRNA Expression and Secretion by Interleukin-1,Interleukin-6, and Interferon-g in Resident and Stimulated Murine Peritoneal Macroph…
2002
The complement system plays an important role in the humoral immune response. Activation of the classical complement pathway is mediated by its subcomponent, C1q. Among the main C1q-synthesising tissues, macrophages have been attributed as a source of particular importance. We investigated the effects of cytokines (IL-1, IL-6 and Interferon-gamma) on local C1q mRNA expression and C1q secretion in resident and in thioglycollate-stimulated murine peritoneal macrophages in vitro. The macrophages were isolated from murine peritoneal lavage fluid, maintained in culture and incubated with the cytokines. Among the cytokines, only IL-6 had a stimulatory effect on C1q production (25% increase vs. co…
CD4-mediated functional activation of human CD4+CD25+ regulatory T cells
2007
Naturally occurring CD4(+)CD25(+)FoxP3(+) regulatory T cells (CD25(+) Tregs) constitute a specialized population of T cells that is essential for the maintenance of peripheral self-tolerance. The immune regulatory function of CD25(+) Tregs depends upon their activation. We found that anti-CD4 antibodies activate the suppressive function of human CD25(+) Tregs in a dose-dependent manner. We demonstrate that CD4-activated CD25(+) Tregs suppress the proliferation of CD4(+) and CD8(+) T cells, their IL-2 and IFN-gamma production as well as the capacity of CD8(+) T cells to re-express CD25. By contrast, anti-CD4 stimulation did not induce suppressive activity in conventional CD4(+) T cells. Thes…
Secreted proteophosphoglycan of Leishmania mexicana amastigotes activates complement by triggering the mannan binding lectin pathway.
1997
Cutaneous lesions induced by infection of mice with the protozoan parasite, Leishmania mexicana, contain abundant amounts of a high molecular mass proteophosphoglycan (PPG), which is secreted by the amastigote stage residing in phagolysosomes of macrophages and can then be released into the tissue upon rupture of the infected cells. Amastigote PPG forms sausage-shaped but soluble particles and belongs to a novel class of serine-rich proteins that are extensively O-glycosylated by phosphooligosaccharides capped by mannooligosaccharides. The purified molecule is shown here to efficiently activate complement (C) and deplete hemolytic activity of normal serum and may prevent the opsonization of…
Clinical resistance to the kinase inhibitor PKC412 in acute myeloid leukemia by mutation of Asn-676 in the FLT3 tyrosine kinase domain.
2005
Activating mutations in the FLT3 tyrosine kinase (TK) occur in approximately 35% of patients with acute myeloid leukemia (AML). Therefore, targeting mutated FLT3 is an attractive therapeutic strategy, and early clinical trials testing FLT3 TK inhibitors (TKI) showed measurable clinical responses. Most of these responses were transient; however, in a subset of patients blast recurrence was preceded by an interval of prolonged remission. The etiology of clinical resistance to FLT3-TKI in AML is unclear but is of major significance for the development of future therapeutic strategies. We searched for mechanisms of resistance in 6 patients with AML who had relapses upon PKC412 treatment. In an …
A central role for Notch in effector CD8(+) T cell differentiation.
2014
Activated CD8(+) T cells choose between terminal effector cell (TEC) or memory precursor cell (MPC) fates. We found that the signaling receptor Notch controls this 'choice'. Notch promoted the differentiation of immediately protective TECs and was correspondingly required for the clearance of acute infection with influenza virus. Notch activated a major portion of the TEC-specific gene-expression program and suppressed the MPC-specific program. Expression of Notch was induced on naive CD8(+) T cells by inflammatory mediators and interleukin 2 (IL-2) via pathways dependent on the metabolic checkpoint kinase mTOR and the transcription factor T-bet. These pathways were subsequently amplified d…
Murine model of interstitial cytomegalovirus pneumonia in syngeneic bone marrow transplantation: persistence of protective pulmonary CD8-T-cell infil…
2000
ABSTRACTInterstitial pneumonia (IP) is a severe organ manifestation of cytomegalovirus (CMV) disease in the immunocompromised host, in particular in recipients of bone marrow transplantation (BMT). Diagnostic criteria for the definition of CMV-IP include clinical evidence of pneumonia together with CMV detected in bronchoalveolar lavage or lung biopsy. We have used the model of syngeneic BMT and simultaneous infection of BALB/c mice with murine CMV for studying the pathogenesis of CMV-IP by controlled longitudinal analysis. A disseminated cytopathic infection of the lungs with fatal outcome was observed only when reconstituting CD8 T cells were depleted. Neither CD8 nor CD4 T cells mediated…
Protection from graft-versus-host disease by HIV-1 envelope protein gp120-mediated activation of human CD4+CD25+ regulatory T cells.
2009
AbstractNaturally occurring CD4+CD25+ regulatory T cells (Tregs) represent a unique T-cell lineage that is endowed with the ability to actively suppress immune responses. Therefore, approaches to modulate Treg function in vivo could provide ways to enhance or reduce immune responses and lead to novel therapies. Here we show that the CD4 binding human immunodeficiency virus-1 envelope glycoprotein gp120 is a useful and potent tool for functional activation of human Tregs in vitro and in vivo. Gp120 activates human Tregs by binding and signaling through CD4. Upon stimulation with gp120, human Tregs accumulate cyclic adenosine monophosphate (cAMP) in their cytosol. Inhibition of endogeneous cA…
Increased susceptibility of complement factor B/C2 double knockout mice and mannan-binding lectin knockout mice to systemic infection with Candida al…
2008
Candida albicans is the major cause of systemic fungal infections in immunocompromised patients. We investigated the susceptibility of mice deficient in complement factor B and C2 (Bf/C2-/-), C1q (C1qa-/-), and mannan-binding lectin (MBL)-A (MBL-A) and MBL-C (MBL-A/C-/-) to systemic infection with C. albicans. Animals were infected i.p. with 10(8)C. albicans blastoconidia and monitored for mortality. Bf/C2-/- mice showed high mortality (over 90%) within the study period of 3 weeks. In contrast, mortality in C1qa-/- mice was below 15% whereas that of MBL-A/C-/- mice was 40% (P0.001). Intravenous infection of mice with 8x10(5) blastoconidia resulted in the same trend with Bf/C2-/- mice being …