Search results for "Immune system"
showing 10 items of 2885 documents
Fulfilling the dream: tolerogenic dendritic cells to treat multiple sclerosis.
2012
Autoimmune diseases including multiple sclerosis (MS) are the result of an imbalanced immune tolerance network. Dendritic cells (DCs) are key players in both initiating immunity (immunogenic DCs) and regulating immune responses (tolerogenic DCs = tolDCs) and are potential targets for the treatment of MS. While the immunogenic potential of DCs in fighting infection and cancer has been well established, approaches that exploit their tolerogenic features to promote transplantation tolerance and autoimmunity have emerged only more recently. TolDCs usually maintain antigen-specific T-cell tolerance either directly by inducing anergy, apoptosis, or phenotype skewing or indirectly by induction of …
Cell Contact–Dependent Priming and Fc Interaction with CD32+ Immune Cells Contribute to the TGN1412-Triggered Cytokine Response
2014
Abstract Following inconspicuous preclinical testing, the superagonistic anti-CD28 mAb TGN1412 was applied to six study participants who all developed a devastating cytokine storm. We verified that TGN1412 treatment of fresh PBMCs induced only moderate responses, whereas restoration of tissue-like conditions by high-density preculture (HDC) allowed vigorous cytokine production. TGN1412 treatment of T cells isolated from HDC-PBMCs induced moderate cytokine responses, which upon additional anti-IgG crosslinking were significantly boosted. Moreover, coincubation of TGN1412-treated T cells with B cells expressing the intermediate affinity Fcγ receptor IIB (CD32B), or coincubation with CD32B+ tr…
The role of accessory cells in polyclonal T cell activation. I. Both induction of interleukin 2 production and of interleukin 2 responsiveness by con…
1983
Recent studies from other laboratories have shown that concanavalin A (Con A) acts at two separate steps in polyclonal T cell activation: interleukin 2 (IL2) production, and induction of responsiveness to IL2. Using a combination of techniques for the depletion of accessory cells from lymph node T cells, we have investigated which of these steps, if not both, is responsible for the known requirement for accessory cells in the Con A response. It was found that with increasing T cell purification, first the ability is lost to produce sufficient levels of endogenous IL2, whereas induction of IL2 responsiveness can still take place. Further removal of accessory cells however yields a population…
Targeting transcription factor Stat4 uncovers a role for interleukin-18 in the pathogenesis of severe lupus nephritis in mice
2011
Polymorphisms in the transcription factor Stat4 gene have been implicated as risk factors for systemic lupus erythematosus. Although some polymorphisms have a strong association with autoantibodies and nephritis, their impact on pathophysiology is still unknown. To explore this further we used signal transducers and activators of transcription 4 (Stat4) knockout MRL/MpJ-Fas(lpr)/Fas(lpr) (MRL-Fas(lpr)) mice and found that they did not differ in survival or renal function from Stat4-intact MRL-Fas(lpr) mice. Circulating interleukin (IL)-18 levels, however, were elevated in Stat4-deficient compared to Stat4-intact mice, suggesting that this interleukin might contribute to the progression of l…
Fast recovery with etanercept in patients affected by polymyalgia rheumatica and decompensated diabetes: a case-series study
2008
We enrolled nine consecutive patients affected by newly diagnosed polymyalgia rheumatica and decompensated diabetes mellitus. All patients were treated with etanercept (25 mg twice weekly) and prednisone and were followed up to 1 year. At the sixth-month follow-up, etanercept and prednisone were withdrawn. Patients were seen at regular intervals (days 0, 30, 60, 90, 150, 180) and the following variables determined: erythrocytes sedimentation rate, C-reactive protein, fasting serum glucose, pain measured by visual analog scale, and the Health Assessment Questionnaire. Our results indicate that etanercept might have some steroid-sparing effects, but controlled investigations are needed to sup…
Processing and MHC class I presentation of human cytomegalovirus pp65-derived peptides persist despite gpUS2–11-mediated immune evasion
2007
Immune control of human cytomegalovirus (HCMV) infection can be mediated by CD8+cytolytic T lymphocytes (CTL). Adoptive transfer of antiviral CTL confers protection against HCMV reactivation and disease. The tegument protein pp65 and the immediate-early 1 protein (IE1) are recognized to be major CTL targets, even though during productive infection the viral immunoevasion proteins gpUS2–11 act to suppress major histocompatibility complex (MHC) class I-restricted antigen presentation. Thus it was not clear how infected cells could be labelled with antigenic peptides in the face of immunoevasion. We show here that the immunodominant peptide pp65NLVwas presented by MHC class I in cells infected…
Immuno-toxicological Evaluation of the Adjuvant Formulations for Experimental Anti-meningococcal Vaccines without Aluminium Hydroxide
2019
International audience; The proteoliposomes and cochleates are used as adjuvants for vaccines since they are potent immune stimulators. However, the hyper stimulation of the immune system provoked by adjuvants can cause immunetoxicological side effects. The present study was carried out to evaluate the toxic and immuno-toxicological effects of new adjuvants for anti-meningococci vaccines based on neo-proteoliposomes (nPL) and neocochleates (nCh), in Balb/c mice that were administered doses of 15 µg each, over periods of 14 days through intramuscular route and three inoculations with the same doses through intranasal route, every 7 days. The Scanning and Transmission Electron Microscopy show…
Targeting cells of the immune system: mannosylated HPMA–LMA block-copolymer micelles for targeting of dendritic cells
2016
Background: Successful tumor immunotherapy depends on the induction of strong and sustained tumor antigen-specific immune responses by activated antigen-presenting cells (APCs) such as dendritic cells (DCs). Since nanoparticles have the potential to codeliver tumor-specific antigen and DC-stimulating adjuvant in a DC-targeting manner, we wanted to assess the suitability of mannosylated HPMA-LMA block polymers for immunotherapy. Materials & methods: Fluorescence-labeled block copolymer micelles derived from P(HPMA)-block-P(LMA) copolymers and according statistical copolymers were synthesized via RAFT polymerization, and loaded with the APC activator L18-MDP. Both types of copolymers wer…
Biomaterial Surface Hydrophobicity-Mediated Serum Protein Adsorption and Immune Responses.
2019
The nature of the protein corona forming on biomaterial surfaces can affect the performance of implanted devices. This study investigated the role of surface chemistry and wettability on human serum-derived protein corona formation on biomaterial surfaces and the subsequent effects on the cellular innate immune response. Plasma polymerization, a substrate-independent technique, was employed to create nanothin coatings with four specific chemical functionalities and a spectrum of surface charges and wettability. The amount and type of protein adsorbed was strongly influenced by surface chemistry and wettability but did not show any dependence on surface charge. An enhanced adsorption of the …
Pregnancy and periodontal disease: does exist a two-way relationship?
2017
Periodontal disease (PD) is an inflammatory disease of the tissues supporting the teeth. PD affects 65 million adults over the age of 30 years in the USA, and worldwide 5 to 70% of adults. Women who develop PD during pregnancy, itâs estimated 1 woman in 5, may have a higher risk of adverse pregnancy outcomes. PD during pregnancy starts by dental plaque and is increased by the action of pregnancy hormones. In order to study the effect of PD on adverse pregnancy outcomes, we have performed this narrative review summarising the current studies about the influence of PD on pregnancy. Periodontal pockets are a reservoir of oral microbiota. Modifications in oral microbiota may be considered as …