PubMed Journal Database | European journal of immunology 
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Showing PubMed Articles 1–25 of 297 from European journal of immunology
Pairing of T-cell receptor chains via emulsion PCR.
Our ability to analyze adaptive immunity and engineer its activity has long been constrained by our limited ability to identify native pairs of heavy-light antibody chains and alpha-beta T-cell receptor (TCR) chains - both of which comprise coupled "halves of a key", collectively capable of recognizing specific antigens. Here we report a cell-based emulsion RT-PCR approach that allows the selective fusion of the native pairs of amplified TCR alpha and beta chain genes for complex samples. A new type of PCR...
CEACAM1 on activated NK cells inhibits NKG2D-mediated cytolytic function and signaling.
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed on activated natural killer (NK) cells wherein it inhibits lysis of CEACAM1-bearing tumor cell lines. The mechanism for this is unknown. Here we show that interleukin-2-induced expression of CEACAM1 on both mouse and primary human NK cells impairs the ability of NKG2D to stimulate cytolysis of CEACAM1-bearing cells. This process requires the expression of CEACAM1 on the NK cell and on the tumor cells, which is consistent with t...
Plasmodium spp. parasites, the causative agents of malaria, survive and replicate in human hosts by modulating host protective immune responses. In a rodent model, malaria manifests as a severe splenomegaly, with infiltration of cells and lymphoproliferation as major contributing factors of the immunopathology. However, the cellular contents and the functions of these cells have not been well studied. Here, we report that Plasmodium berghei infection of mice leads to massive recruitment of mesenchymal stem...
The T-cell repertoire depends on intrathymic genetic rearrangement events in the T-cell receptor (TCR) locus, followed by positive and negative selection. The repertoire thus generated is highly diverse, but recent data indicate that the recombination of gene segments is less stochastic than previously suggested. Very little is known of the junctional complementarity determining region 3 (CDR3), which is to a large degree not germline-encoded. We have analyzed the development of the human TCR β CDR3 repert...
Tripartite motif (TRIM) 22 plays an important role in IFN-mediated antiviral activity. We previously demonstrated that IRF-1 was crucial for constitutive and IFN-induced TRIM22 expression via binding to a special cis-element named 5' extended IFN-stimulating response element (5'eISRE). Here, we further investigate the molecular mechanisms of TRIM22 with a focus on the co-activators of IRF-1. Using an in vitro DNA affinity binding assay and an in vivo chromatin immunoprecipitation assay, we found that IFN-γ...
Here we describe a novel method via which ex vivo cultured mouse bone marrow-derived eosinophils (bmEos) can be adoptively transferred into recipient mice in order to study receptor-dependent recruitment to lung tissue in vivo. Intratracheal instillation of hCCL24 prior to introduction of bmEos via tail vein injection resulted in a ∼fourfold increase in Siglec F positive/CD11c negative eosinophils in the lungs of eosinophil-deficient ΔdblGATA recipient mice compared with controls. As anticipated, bmEos g...
Invariant natural killer T (iNKT) cell exhaustion in sarcoidosis.
Invariant natural killer T (iNKT) cells are integral components of immune responses during many chronic diseases, yet their surface phenotypes, subset distribution, and polyfunctional capacity in this environment are largely unknown. Therefore, using flow cytometry, we determined iNKT-cell phenotypic and functional characteristics in subjects with the chronic inflammatory disease sarcoidosis and matched controls. We found that sarcoidosis subjects displayed lower iNKT-cell frequencies, which correlated with...
CD40-CD40L interactions are important for both antigen-dependent B-cell differentiation and effector and memory T-cell formation. The prevailing view is that CD40L is expressed on activated CD4(+) T cells, which enables them to provide help to high-affinity B cells in germinal centers and to license DCs for efficient induction of CD8(+) T-cell responses. Interestingly, CD8(+) T cells themselves can also express CD40L and, in this issue of the European Journal of Immunology, Thiel and colleagues [Eur. J. Imm...
Vitamin A notches up CD11b(hi) dendritic cell development.
Vitamin A and its metabolite retinoic acid influence various aspects of immunity. Although the capacity of vitamin A to condition intestinal CD103(+) dendritic cells (DCs) to imprint tissue-specific homing programs onto activated lymphocytes is well documented, it is unclear whether vitamin A also regulates DC populations in other tissues. A study published in this issue of the European Journal of Immunology [Eur. J. Immunol. 2013. 43: XXXX-XXXX] now demonstrates that vitamin A exerts profound effects on th...
Several groups have shown that detection of microbial components by Toll-like receptors (TLRs) on hematopoietic stem and progenitor cells (HSPCs) instructs myeloid cell generation, raising interest in the possibility of targeting TLRs on HSPCs to boost myelopoiesis. However, although "TLR-derived" cells exhibit myeloid cell characteristics (phagocytosis, cytokine production, antigen presentation), it isn't clear whether they are functionally equivalent to macrophages derived in the absence of TLR activation...
Multiple sclerosis (MS) is an autoimmune-mediated inflammatory disease characterized by multifocal areas of demyelination. Experimental evidence indicates that A2A adenosine receptors (ARs) play a pivotal role in the inhibition of inflammatory processes. The aim of this study was to investigate the contribution of A2A ARs in the inhibition of key pro-inflammatory mediators for the pathogenesis of MS. In lymphocytes from MS patients, A1 , A2A , A2B and A3 ARs were analyzed by using RT-PCR, western blotting,...
IFN-β therapy modulates B-cell and monocyte crosstalk via TLR7 in multiple sclerosis patients.
The implication of B lymphocytes in the immunopathology of multiple sclerosis (MS) is increasingly recognized. Here we investigated the response of B cells to IFN-β, a first-line therapy for relapsing-remitting MS patients, upon stimulation with TLR. IFN-β restored the frequency of TLR7-induced IgM and IgG-secreting cells in MS patients to the levels found in healthy donors (HDs), showing a specific deficiency in TLR7 pathway. However, no difference was observed in the TLR9 response. Furthermore, in MS-de...
Viral double-stranded RNA (dsRNA) mimetics have been explored in cancer immunotherapy to promote antitumoral immune response. Polyinosine-polycytidylic acid (poly I:C) and Polyadenylic-polyuridylic acid (poly A:U) are synthetic analogs of viral dsRNA and strong inducers of type I Interferon (IFN). We describe here a novel effect of dsRNA analogs on cancer cells: besides their potential to induce cancer cell apoptosis through an IFN-β autocrine loop, dsRNA-elicited IFN-β production improves dendritic cell...
Positive selection of self antigen-specific CD8(+) T cells by hematopoietic cells.
In contrast to thymic epithelial cells, which induce the positive selection of conventional CD8(+) T cells, hematopoietic cells (HCs) select innate CD8(+) T cells whose antigen specificity is not fully understood. Here we show that CD8(+) T cells expressing an H-Y antigen-specific transgenic (Tg) TCR were able to develop in mice in which only HCs expressed MHC class I, when HCs also expressed the H-Y antigen. These HC-selected self-specific CD8(+) T cells resemble innate CD8(+) T cells in wild-type mice in...
Multiple sclerosis (MS) is an inflammatory central nervous system (CNS) disorder which typically occurs in early adulthood and rarely in children. Here we tested whether functional maturation of innate immune cells may determine susceptibility to CNS autoimmune disease in experimental autoimmune encephalomyelitis (EAE). Two week-old mice were resistant to active EAE, which causes fulminant paralysis in adult mice; this resistance was associated with an impaired development of Th1 and Th17 cells. Resistant,...
Defects of leukocyte migration in primary immunodeficiencies.
This Viewpoint gives an overview of the inherited disorders that are characterized by defects of leukocyte trafficking. Three paradigmatic diseases have been selected: WHIM, Wiskott-Aldrich and LAD syndromes. These conditions encompass defects in the steps that are required for leukocyte motility: from the response to chemokines, which is altered in WHIM syndrome, to the impairment of leukocyte adhesion and migration found in LAD syndrome, and finally to abnormal actin filament formation, which is affected...
Traumatic brain injury induces macrophage subsets in the brain.
Traumatic brain injury (TBI) elicits innate inflammatory responses that can lead to secondary brain injury. To better understand the mechanisms involved in TBI-induced inflammation, we examined the nature of macrophages responding to TBI in mice. In this model, brain macrophages were increased >20-fold the day after injury and >77-fold four days after injury in the ipsilateral hemisphere compared with sham controls. TBI macrophage subsets were identified by using a reporter mouse strain (YARG) that expresse...
Alarmin-induced cell migration.
Alarmins are endogenous, constitutively available, damage-associated molecular patterns (DAMPs) that upon release can mobilize and activate various leukocytes for the induction of innate and adaptive immune responses. For our immune system to function appropriately, it relies on navigating various leukocytes to distinct places at the right time. The direction of cell migration is determined by chemotactic factors that include classical chemoattractants, chemokines, certain growth factors, and alarmins. This...
The NLRP3 inflammasome is a cytoplasmic protein complex that mediates inflammatory responses to a broad array of danger signals. The inflammasome drives caspase-1 activation and promotes secretion of the pro-inflammatory cytokines IL-1β and IL-18, and might also participate in other cellular processes. Here we tried to identify new pathways regulated by the NLRP3 inflammasome in murine DCs in response to monosodium urate (MSU) crystals. Using a transcriptomic approach, we found that DCs from Nlrp3(-/-) mic...
Although the development of T-cell subsets is mainly regulated by a master transcriptional regulator and phosphorylation of the signal transducer and activator of transcription (STAT) protein in response to distinct cytokine stimulation, accumulating data indicate that other signaling pathways are also involved in regulating or fine-tuning T-cell lineage commitment. In this report, we investigated the role of ERK MAPK (Extracellular signal-regulated kinases, Mitogen-activated protein kinase) in T helper 17...
Following antigen/IgE-mediated aggregation of high affinity IgE-receptors (FcεRI), mast cells (MCs) degranulate and release inflammatory mediators leading to the induction of allergic reactions including anaphylaxis. Migration of MCs to resident tissues and sites of inflammation is regulated by tissue chemotactic factors such as stem cell factor (SCF (KIT ligand)). Despite inducing similar early signaling events to antigen, chemotactic factors, including SCF, produce minimal degranulation in the absence of...
Thymus-homing dendritic cells in central tolerance.
Central tolerance is critical in establishing a peripheral T-cell repertoire purged of functional autoreactive T cells. One of the major requirements for effective central tolerance is the presentation of self and other innocuous antigens (Ags), including food, gut flora or airway allergens, to developing T cells in the thymus. This seemingly challenging task can be mediated in some cases by ectopic expression of tissue-specific Ags by thymic epithelial cells, or by entry of systemic blood borne Ags into th...
Immunoregulatory mechanisms within periapical lesions (PLs) are as yet unexplored. Considering the crucial role of DCs in controlling the immune response within PLs, the immunomodulatory properties of mesenchymal stem cells (MSCs), and the co-localisation of MSCs and DCs in situ, we wondered whether MSCs from PLs modulate the development and functions of DCs. Using a model of monocyte-derived DCs, we showed that PL-MSCs inhibited differentiation of DCs via soluble factors, of which IL-6 had a minor effect,...
Synthetic oligonucleotides (ODN) expressing CpG motifs mimic the ability of bacterial DNA to trigger the innate immune system via TLR9. Plasmacytoid dendritic cells (pDCs) make a critical contribution to the ensuing immune response. This work examines the induction of anti-viral (IFN-β) and pro-inflammatory (IL-6) cytokines by CpG stimulated human pDCs and the human CAL-1 pDC cell line. Results show that interferon regulatory factor-5 (IRF-5) and NF-κB p50 are key co-regulators of IFN-β and IL-6 expressi...
Survivin, an inhibitor of apoptosis family molecule, has been proposed as a crucial intermediate in the signaling pathways leading to T-cell development, proliferation, and expansion. However, the importance of survivin to T-cell-driven inflammatory responses has not been demonstrated. Here, we show that survivin transgenic mice exhibit an increased antigen-driven Th2 lung inflammation and that constitutive expression of survivin reversed the defective lung inflammation even in the absence of OX40 costimula...
