Cells meeting our immunophenotypic criteria of endothelial cells are large platelets.

Background: Circulating endothelial cells (CEC) are shed from damaged vasculature, making them a rational choice to serve as surrogate marker for vascular damage. Currently, various techniques and CEC definitions are in use, and their standardization and validation is needed. A flow cytometric single platform assay defining CEC as forward light scatter (FSC)(low-to-intermedate), sideward light scatter (SSC)(low), CD45(-), CD31(++) and CD146(+) is a promising approach to enumerate CEC because of its simplicity (Mancuso et al.

An essential role for dendritic cells in human and experimental allergic rhinitis.

Background: In allergic rhinitis (AR) CD4(+) T(H)2 lymphocytes control inflammation by secreting T(H)2 cytokines, but little is known about how these cells are activated to cause disease.

Objective: We sought to study the contribution of antigen-presenting dendritic cells (DCs) in activating T(H)2 cells and controlling allergic inflammation.

Methods: Nasal mucosal biopsy specimens were taken from patients with house dust mite allergy and perennial AR and healthy control subjects.

Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function.

Airway DCs play a crucial role in the pathogenesis of allergic asthma, and interfering with their function could constitute a novel form of therapy. The sphingosine 1-phosphate receptor agonist FTY720 is an oral immunosuppressant that retains lymphocytes in lymph nodes and spleen, thus preventing lymphocyte migration to inflammatory sites. The accompanying lymphopenia could be a serious side effect that would preclude the use of FTY720 as an antiasthmatic drug.

Contribution of the PD-1 ligands/PD-1 signaling pathway to dendritic cell-mediated CD4+ T cell activation.

Dendritic cells (DC) are extremely proficient inducers of naïve CD4+ T cell activation due to their high expression level of peptide-MHC and an array of accessory molecules involved in cell migration, adhesion and co-signaling, including PD-1 ligand 1 (PD-L1) and PD-1 ligand 2 (PD-L2). Whether PD-L1 and PD-L2 have a stimulatory or inhibitory function is a matter of debate, and could be partially dependent on the model system used. In this study we examined the role of PD-L1 and PD-L2 expressed by DC in naïve CD4+ T cell activation in a more physiologically relevant model system, using OVA-specific T cells in combination with various levels of TCR stimulation.

Recent progress in the biology of airway dendritic cells and implications for understanding the regulation of asthmatic inflammation.

Dendritic cells (DCs) are crucial in determining the outcome of antigen encounter and integrating signals derived from the antigen, its inflammatory context, and the host environment into a signal that can be read by naive T cells in the lymphoid tissues and by effector T cells in peripheral tissues. Airway DC subsets, however, induce different types of immune responses, with plasmacytoid DCs promoting tolerance and myeloid DCs inducing immunity. We also propose that airway DCs are not only crucial for sensitization to inhaled antigens, leading to allergy, but also play a crucial role in established inflammation and therefore represent a therapeutic target to prevent the development of airway diseases.

Alveolar macrophage in the driver's seat.

Although alveolar macrophages are normally quiescent to prevent damaging the alveoli, in this issue of Immunity, Takabayshi et al. (2006) demonstrate that alveolar macrophages can self-regulate their function on demand to mount an appropriate immune response.

Mesothelioma environment comprises cytokines and T-regulatory cells that suppress immune responses.

Malignant mesothelioma is a cancer with dismal prognosis. The objective of the present study was to address the role of the immune system, tumour micro-environment and potential immunosuppression in mesothelioma. Expression profiles of 80 cytokines were determined in the supernatant of mesothelioma cell lines and the original patient's pleural effusion.

Sterility testing of platelet concentrates prepared from deliberately infected blood donations.

Background: In general the bacterial count in freshly donated blood is low and even lower in the corresponding platelet concentrates (PCs). By use of flow cytometry (FACS) for sterility testing, the reliability of early versus later sampling times was evaluated.

Study Design And Methods: Blood donations were spiked with various numbers of Staphylococcus epidermidis, Staphylococcus aureus, Bacillus cereus, and Klebsiella pneumoniae.

An unexpected role for the anaphylatoxin C5a receptor in allergic sensitization.

The anaphylatoxins complement component 3a and 5a (C3a and C5a, respectively) are classically seen as proinflammatory mediators of allergic asthma that recruit inflammatory cells, induce edema, and cause bronchoconstriction. A few years ago, controversy arose when it was shown that C5-deficient mice were more susceptible to experimental asthma compared with C5-sufficient mice. In a study by Köhl et al.

Basics of flow cytometry-based sterility testing of platelet concentrates.

Background: Flow cytometry (FACS) is a common technique in blood banking. It is used, for example, for the enumeration of residual white blood cells in plasma and in cellular blood products. It was investigated whether it can also be applied for sterility testing of buffy coat-derived platelet concentrates (PCs).

Vaccination of chicken embryos with escape mutants of La Sota Newcastle disease virus induces a protective immune response.

To reduce the embryonic pathogenicity of Newcastle disease virus (NDV), escape mutants of the La Sota strain were produced with selected monoclonal antibodies. Immunoselection resulted in the elimination of an epitope by single amino acid substitution (F and HN molecule) or in a conformational change (HN molecule). The embryonic pathogenicity of these escape mutants was reduced and their dose was optimised for in ovo vaccination.

Dendritic cells in asthma: a function beyond sensitization.

Allergic asthma is one of the most common chronic diseases in western society, characterized by variable airway obstruction, mucus hypersecretion and infiltration of the airway wall with T-helper type 2 (Th2) cells, eosinophils and mast cells. If we are to devise new causal therapies for this disease, it is important to elucidate how Th2 cells are activated and respond to intrinsically harmless allergens. Dendritic cells (DCs) are the most important antigen-presenting cells in the lung and are mainly recognized for their exceptional potential to generate a primary immune response and sensitization to aeroallergens.

Respiratory viral infections and asthma pathogenesis: a critical role for dendritic cells?

Background: Respiratory viral infections can influence the course of asthma at different time points. Severe respiratory viral infections during early age are associated with a higher prevalence of asthma in later childhood. In established asthma, viral infections are a frequent cause of asthma exacerbation.

Modification of dendritic cell function as a tool to prevent and treat allergic asthma.

Atopic asthma is a chronic inflammatory disease of the airways, characterized by airway hyperreactivity and mucus hypersecretion that result in intermittent airway obstruction. This chronic inflammation is the result of an aberrant Th2-mediated response to innocuous environmental proteins. The prevalence of this disease has increased dramatically in the industrialized world in the last decades.

Dendritic cell subsets and immune regulation in the lung.

The lung is continuously exposed to inhaled particles, microbes and harmless antigens to which either immunity or tolerance is induced. Dendritic cells are mainly recognized for their extraordinary capacity to induce a primary immune response in the lung. Recent evidence suggests that particular subsets of DCs are essential in the decision between immunity or tolerance.

Treatment of experimental asthma by decoy-mediated local inhibition of activator protein-1.

Rationale: Asthma is associated with increased expression of a typical array of genes involved in immune and inflammatory responses, including those encoding the prototypic Th2 cytokines interleukin (IL) 4, IL-5, and IL-13. Most of these genes contain binding sites for activator protein-1 (AP-1) within their promoter and are therefore believed to depend on AP-1 for their expression, suggesting that this transcription factor could be of particular importance in asthma pathophysiology.

Objective: To clarify the role of AP-1 in the effector phase of pulmonary allergy.

Highly pathogenic H5N1 influenza virus in smuggled Thai eagles, Belgium.

We report the isolation and characterization of a highly pathogenic avian influenza A/H5N1 virus from Crested Hawk-Eagles smuggled into Europe by air travel. A screening performed in human and avian contacts indicated no dissemination occurred. Illegal movements of birds are a major threat for the introduction of highly pathogenic avian influenza.

Surfactant pretreatment ameliorates ischemia-reperfusion injury of the lung.

Objective: To investigate whether surfactant pretreatment provides lung protection in an animal model of lung ischemia-reperfusion injury (LIRI).

Methods: Male Sprague-Dawley rats (n=100) were randomised to receive intratracheally administered surfactant or no pretreatment. One hour thereafter, animals underwent 120min of warm ischemia of the left lung, or were sham-operated.

In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma.

Although dendritic cells (DCs) play an important role in sensitization to inhaled allergens, their function in ongoing T helper (Th)2 cell-mediated eosinophilic airway inflammation underlying bronchial asthma is currently unknown. Here, we show in an ovalbumin (OVA)-driven murine asthma model that airway DCs acquire a mature phenotype and interact with CD4(+) T cells within sites of peribronchial and perivascular inflammation. To study whether DCs contributed to inflammation, we depleted DCs from the airways of CD11c-diphtheria toxin (DT) receptor transgenic mice during the OVA aerosol challenge.

Immunotherapy of murine malignant mesothelioma using tumor lysate-pulsed dendritic cells.

Rationale: Exploiting the immunostimulatory capacities of dendritic cells holds great promise for cancer immunotherapy. Currently, dendritic cell-based immunotherapy is evaluated clinically in a number of malignancies, including melanoma and urogenital and lung cancer, showing variable but promising results.

Objective: To evaluate if pulsed dendritic cells induce protective immunity against malignant mesothelioma in a mouse model.

Dendritic cells and the regulation of the allergic immune response.

Studies in mouse models of asthma have revealed a critical role for airway dendritic cells in the induction of Th2 sensitization to inhaled allergens. Under some conditions, subsets of dendritic cells can also induce tolerance or Th1 responses to the same allergens, depending on the context in which the antigen is seen. This article discusses various aspects of DC biology as it relates to allergic sensitization and also provides a summary of the recent evidence that dendritic cells function beyond sensitization.

Differential capacity of CD8+ alpha or CD8- alpha dendritic cell subsets to prime for eosinophilic airway inflammation in the T-helper type 2-prone milieu of the lung.

Background: Different subsets of dendritic cells (DCs), identified in mouse spleen by their differential expression of CD8 alpha, can induce different T-helper (Th) responses after systemic administration. CD8 alpha(-) DCs have been shown to preferentially induce Th type 2 (Th2) responses whereas CD8 alpha(+) DCs induce Th1 responses.

Objective: To study if these DC subsets can still induce different Th responses in the Th2-prone milieu of the lung and differentially prime for eosinophilic airway inflammation, typical of asthma.

Proinflammatory bacterial peptidoglycan as a cofactor for the development of central nervous system autoimmune disease.

Upon stimulation by microbial products through TLR, dendritic cells (DC) acquire the capacity to prime naive T cells and to initiate a proinflammatory immune response. Recently, we have shown that APC within the CNS of multiple sclerosis (MS) patients contain peptidoglycan (PGN), a major cell wall component of Gram-positive bacteria, which signals through TLR and NOD. In this study, we report that Staphylococcus aureus PGN as a single component can support the induction of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model for MS.

The interplay of dendritic cells, Th2 cells and regulatory T cells in asthma.

Dendritic cells are essential for Th2 differentiation of naive CD4+ T cells in response to aeroallergens, and in recent years it has been well established that these cells play a pivotal role in the initiation phase of allergic asthma. Dendritic cells are also crucial for maintaining eosinophilic airway inflammation by controlling the recruitment and activation of primed Th2 cells in the lung. A picture is emerging wherein the balance of pathogenic Th2 cells and regulatory T cells is tuned by dendritic cells not only at the initiation but also at the effector stage of the allergic immune response.

Dendritic cells retrovirally overexpressing IL-12 induce strong Th1 responses to inhaled antigen in the lung but fail to revert established Th2 sensitization.

It has been postulated that low-level interleukin (IL)-12 production of antigen-presenting cells is associated with the risk of developing atopic asthma. To study the relationship between IL-12 production capacity of dendritic cells (DCs) and development of T helper type 2 (Th2) responses in the lung, we genetically engineered DCs to constutively overexpress bioactive IL-12. Retrovirally mediated overexpression of IL-12 in DCs strongly polarized naive ovalbumin (OVA)-specific CD4+ T cells toward Th1 effector cells in vitro.