Cord Blood Derived CD4+CD25high T Cells Become Functional Regulatory T Cells upon Antigen Encounter

Background: Upon antigen exposure, cord blood derived T cells respond to ubiquitous environmental antigens by high proliferation. To date it remains unclear whether these “excessive” responses relate to different regulatory properties of the putative T regulatory cell (Treg) compartment or even expansion of the Treg compartment itself

Szabályos és rendhagyó ragozású szavak pszicholingvisztikai vizsgálata

Jelen kutatás fő célja a szabályos és rendhagyó ragozású szavak összehasonlítása ragozott szóterjedelem tesztek és reakcióidő feladat segítségével. A vizsgálat alapkérdése, hogy a rendhagyó ragozású szavak esetében egészleges tárolás valósul-e meg, vagy hasonlóan képezzük őket, mint a szabályos alakokat. További cél az online (menetközbeni) feldolgozás és a memória összefüggésének feltárása. A kutatásban 37 egészséges, átlagos munkamemóriájú egyetemista vett részt, 8 férfi és 29 nő. A vizsgálati alanyok egy szóvisszamondási és egy szónemszó lexikális döntési feladatban vettek részt. Míg a kísérleti személyek a szónemszó döntési feladatban jobb eredményt értek el a szabályos ragozású szavak esetén, addig a memóriafeladatban nincs számottevő különbség a szabályos és a rendhagyó alakok között. Eredményeink alapján úgy tűnik, hogy a rendhagyó ragozású szavakat hasonlóan képezzük, mint a szabályos ragozású szavakat, tehát az olyan gazdag alaktannal rendelkező nyelvek esetében, ahol az inflexiós rag azonosítható a rendhagyó szavak esetén is, dekompozíció fog megvalósulni

Fc-Epsilon-RI, the High Affinity IgE-Receptor, Is Robustly Expressed in the Upper Gastrointestinal Tract and Modulated by Mucosal Inflammation

Background: The role of the high affinity IgE receptor, FcεRI, in IgE-mediated immune responses of the gastrointestinal (GI) mucosa is poorly understood. Currently, a detailed characterization of FcεRI expression throughout the human gut is lacking. The aim of this study was to define the expression pattern of FcεRI in the GI tract. Methods/Principal Findings: We compared FcεRI expression in children with gastritis/esophagitis (n = 10), celiac disease (n = 10), inflammatory bowel disease (IBD) (n = 9), and normal mucosa (n = 5). The α–subunit of FcεRI (FcεRIα), detected by immunohistochemistry, was found on cells infiltrating the mucosa of the esophagus, the stomach, and the duodenum, but was rarely detected in more distal sections of the GI tract. Accordingly, quantitative RT-PCR analysis on esophagus, stomach, duodenum, colon, and rectum biopsies revealed that FcεRIα and -β expression levels decreased towards the distal intestine. mRNA transcripts of the common Fc-receptor-γ chain were present in the entire GI mucosa. Double-immunofluorescence staining of esophageal specimens confirmed that FcεRIα was expressed on intraepithelial mast cells and Langerhans cells. The mRNA expression levels of the α, β, and γ subunits of FcεRI did not correlate with total serum IgE but were associated with mucosal inflammation. Conclusion/Significance: Our data define the upper GI tract as the main site for IgE-mediated immune activation via FcεRI. Tissue mRNA levels of FcεRIα are regulated by inflammatory conditions rather than serum IgE, indicating that FcεRI might also play a role in pathologies other than allergy

Effect of Heating and Glycation on the Allergenicity of 2S Albumins (Ara h 2/6) from Peanut

Although no effect of processing on T-cell reactivity was observed, heat induced denaturation reduced the IgE reactivity and subsequent functionality of Ara h 2/6. Conversely, Ara h 2 and 6 purified from roasted peanut retained the structure and IgE reactivity/functionality of the native protein which may explain the allergenic potency of this protein. Through detailed molecular study and allergenicity assessment approaches, this work then gives new insights into the effect of thermal processing on structure/allergenicity of peanut proteins

A Soluble Form of the High Affinity IgE Receptor, Fc-Epsilon-RI, Circulates in Human Serum

Soluble IgE receptors are potential in vivo modulators of IgE-mediated immune responses and are thus important for our basic understanding of allergic responses. We here characterize a novel soluble version of the IgE-binding alpha-chain of Fc-epsilon-RI (sFcεRI), the high affinity receptor for IgE. sFcεRI immunoprecipitates as a protein of ∼40 kDa and contains an intact IgE-binding site. In human serum, sFcεRI is found as a soluble free IgE receptor as well as a complex with IgE. Using a newly established ELISA, we show that serum sFcεRI levels correlate with serum IgE in patients with elevated IgE. We also show that serum of individuals with normal IgE levels can be found to contain high levels of sFcεRI. After IgE-antigen-mediated crosslinking of surface FcεRI, we detect sFcεRI in the exosome-depleted, soluble fraction of cell culture supernatants. We further show that sFcεRI can block binding of IgE to FcεRI expressed at the cell surface. In summary, we here describe the alpha-chain of FcεRI as a circulating soluble IgE receptor isoform in human serum

The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients

Novel developments in the mechanisms of immune tolerance to allergens

Allergy is the result of a disbalanced immune response to environmental innocuous antigens. Despite of accumulating data to define the pathomechanisms that take place in case of allergic diseases a detailed understanding of sequence of events that lead to the "normal" scenario of tolerance development are still under debate. Allergen-specific immunotherapy is the only causal treatment of allergic diseases. It modifies the immune response to a particular antigen to achieve tolerance against the symptom-causing allergen. This process is considered to mirror physiological peripheral tolerance induction. A number of immunological changes have been described to occur under allergen immunotherapy, including the generation of allergen-specific regulatory T cells, the induction of allergen-specific IgG4, an increase in the Th1/Th2 cytokine ratio and decreased activation and function of effector cells such as mast cells, basophils and eosinophils

Allergen specific responses in cord and adult blood are differentially modulated in the presence of endotoxins.

BACKGROUND: Endotoxins are common contaminants in allergen preparations and affect antigen-specific cellular responses. Distinct effects of endotoxin on cells in human umbilical cord and adult blood are poorly defined. OBJECTIVES: To examine the effect of endotoxins in allergen preparations on cellular responses in human cord and peripheral blood (PB). METHODS: The endotoxin content in β lactoglobulin (BLG), the peanut allergen Ara h 1 and the major birch pollen allergen Bet v 1 was assessed. Proliferation and cytokine response of mononuclear cells towards contaminated and lipopolysaccharide (LPS)-free allergens were evaluated at different time-points. Fractions of contaminated BLG were generated and assayed on their immuno-stimulatory capacity. The involvement of toll-like receptor (TLR) 2 and 4 was investigated by blocking antibodies and TLR-transfected human embryonic kidney cells. RESULTS: The proliferative response of cord blood (CB)-derived mononuclear cells towards allergen-preparations at day 3 was related to the level of LPS contamination. At day 7, proliferation was also detected in the absence of endotoxin. Cytokine production in CB was strongly affected by the content of endotoxin, TLR-4 dependent and not related to the allergen content. Allergen- and endotoxin-induced proliferative responses were generally significantly higher in CB than in adult blood. CONCLUSION: Endotoxins in allergen preparations confound allergen-specific cellular responses. The impact of these contaminations varies with the blood source (CB vs. PB), the type of allergen and is time- and dose-dependent. Cite this as: T. Eiwegger, E. Mayer, S. Brix, I. Schabussova, E. Dehlink, B. Bohle, V. Barkholt and Z. Szépfalusi, Clinical and Experimental Allergy, 2008 (38) 1627–1634