Search results for "MICE"
showing 10 items of 6027 documents
Enhanced dendritic cell maturation by TNF-alpha or cytidine-phosphate-guanosine DNA drives T cell activation in vitro and therapeutic anti-tumor immu…
2000
Abstract Dendritic cells (DC) manipulated ex vivo can induce tumor immunity in experimental murine tumor models. To improve DC-based tumor vaccination, we studied whether DC maturation affects the T cell-activating potential in vitro and the induction of tumor immunity in vivo. Maturation of murine bone marrow-derived DC was induced by GM-CSF plus IL-4 alone or by further addition of TNF-α or a cytidine-phosphate-guanosine (CpG)-containing oligonucleotide (ODN-1826), which mimics the immunostimulatory effect of bacterial DNA. Flow cytometric analysis of costimulatory molecules and MHC class II showed that DC maturation was stimulated most by ODN-1826, whereas TNF-α had an intermediate effec…
Intrahepatic myeloid-cell aggregates enable local proliferation of CD8+T cells and successful immunotherapy against chronic viral liver infection
2013
Chronic infection is difficult to overcome because of exhaustion or depletion of cytotoxic effector CD8(+) T cells (cytotoxic T lymphoytes (CTLs)). Here we report that signaling via Toll-like receptors (TLRs) induced intrahepatic aggregates of myeloid cells that enabled the population expansion of CTLs (iMATEs: 'intrahepatic myeloid-cell aggregates for T cell population expansion') without causing immunopathology. In the liver, CTL proliferation was restricted to iMATEs that were composed of inflammatory monocyte-derived CD11b(+) cells. Signaling via tumor-necrosis factor (TNF) caused iMATE formation that facilitated costimulation dependent on the receptor OX40 for expansion of the CTL popu…
Efficient homologous prime-boost strategies for T cell vaccination based on virus-like particles.
2005
Induction of high frequencies of specific T cells by vaccination requires prime-boost regimens. To reach optimal immune responses, it is necessary to use different vectors for priming and boosting as e.g. DNA vaccination followed by boosting with a recombinant viral vector. Here, we show that vaccines based on virus-like particles (VLP) displaying peptide epitopes are equally effective to induce CTL responses if used in a homologous or heterologous prime-boost setting. Strikingly, high frequencies (>20% of CD8(+) cells) of protective CTL could be induced and maintained by weekly injection of VLP. Thus, the use of VLP may avoid the requirement for complicated heterologous prime-boost regi…
An innate cell-mediated, murine ulcerative colitis-like syndrome in the absence of nuclear factor of activated T cells.
2004
Abstract Background & Aims: Nuclear factor of activated T cells transcription factors plays a central role in immunity by regulating the expression of multiple cytokines and other regulatory molecules, many of which have been heavily implicated in the pathogenesis of inflammatory bowel disease. However, few studies have directly investigated the nuclear factor of activated T cells proteins in inflammatory bowel disease. We describe here a specific role for nuclear factor of activated T cells c2 in the pathogenesis of murine inflammatory bowel disease. Methods: Mice deficient for nuclear factor of activated T cells c2, recombinase activating gene-2, or both and transgenic or nontransgenic fo…
CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction.
2008
T regulatory (Treg) cells play a role in the suppression of immune responses, thus serving to induce tolerance and control autoimmunity. Here, we explored whether Treg cells influence the immediate hypersensitivity response of mast cells (MCs). Treg cells directly inhibited the FcεRI-dependent MC degranulation through cell-cell contact involving OX40-OX40L interactions between Treg cells and MCs, respectively. When activated in the presence of Treg cells, MCs showed increased cyclic adenosine monophosphate (cAMP) concentrations and reduced Ca2+ influx, independently of phospholipase C (PLC)-γ2 or Ca2+ release from intracellular stores. Antagonism of cAMP in MCs reversed the inhibitory effec…
Unexpected Modulation of Recall B and T Cell Responses after Immunization with Rotavirus-like Particles in the Presence of LT-R192G
2010
LT-R192G, a mutant of the thermolabile enterotoxin of E. coli, is a potent adjuvant of immunization. Immune responses are generally analyzed at the end of protocols including at least 2 administrations, but rarely after a prime. To investigate this point, we compared B and T cell responses in mice after one and two intrarectal immunizations with 2/6 rotavirus-like particles (2/6-VLP) and LT-R192G. After a boost, we found, an unexpected lower B cell expansion measured by flow cytometry, despite a secondary antibody response. We then analyzed CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) and CD4(+)CD25(+)Foxp3(-) helper T cells after in vitro (re)stimulation of mesenteric lymph node cells …
Synergistic activation of dendritic cells by combined Toll-like receptor ligation induces superior CTL responses in vivo.
2006
Toll-like receptors (TLRs) are able to interact with pathogen-derived products and their signals induce the coordinated activation of innate and adaptive immune mechanisms. Dendritic cells (DCs) play a central role in these events. As the different TLRs are able to trigger MyD88/TRIF-dependent and -independent signaling pathways, we wondered if the simultaneous activation of these signaling cascades would synergize with respect to DC activation and induce superior cytotoxic T-lymphocyte (CTL) activity in vivo. We observed that indeed the combined activation of MyD88-dependent and -independent signaling induced by TLR7 and TLR3 ligands provoked a more rapid and more sustained bone marrow–der…
NFATc1 affects mouse splenic B cell function by controlling the calcineurin–NFAT signaling network
2011
Mouse B cells lacking NFATc1 exhibit defective proliferation, survival, isotype class switching, cytokine production, and T cell help.
New therapies for sepsis: focus on the interleukin (IL)12 family member IL27
2007
Sepsis is a severe complication of abdominal infections such as peritonitis and is associated with high mortality. Unfortunately, the molecular mechanisms controlling the development of sepsis are still incompletely understood. Interestingly, the interleukin (IL) 12 family member IL27 seems to play a key role in sepsis. In a murine model of septic peritonitis induced by caecal ligation and puncture (CLP), IL27 levels were found to be strongly induced. Furthermore, mice deficient for the EBI3 subunit of IL27 were resistant to CLP-induced septic peritonitis as compared to wild-type controls. This effect could be suppressed by injection of recombinant IL27. Further studies demonstrated that IL…
Primary in vivo T cell reactivity of NZB grafts in H-2 identical allogenic hosts.
1983
By means of the Simonson GVH-assay and the popliteal lymph node (PLN) assay, the T-cell reactivity of NZB mice against H-2 identical allogenic cells was investigated in vivo and compared to that of normal mice. None of the normal mice did react, but a highly significant NZB response could be demonstrated, which did not depend on differences in Mls antigens. These in vivo results extend previous findings of a T-cell hyperreactivity of NZB mice in primary in vitro reactions. They favour the possibility that the T-cell hyperreactivity might be relevant in vivo in facilitating autoimmune responses.