The role of regulatory T cells in the acquisition of tolerance to food allergens in children

Food allergy is a pathological immune reaction that identifies certain harmless food proteins, usually tolerated by the majority of the people, as a threat. The prevalence of these food allergies is increasing worldwide and currently affects 8% of children. Exacerbated reactions to milk, egg and peanut are the most frequent in the pediatric population. It is well known that allergic diseases are a type 2 T-helper (Th2) immune response, characterized by the elevated production of IgE antibodies. However, little is known about the immune mechanisms responsible for the development of clinical tolerance toward food allergens. Recent studies have suggested the key role of regulatory T cells (Tregs) in controlling allergic inflammation. In this review, we discuss the importance of Tregs in the pathogenesis of food allergy and the acquisition of oral tolerance in children. Further investigation in this area will be crucial for the identification of predictive markers and the development of new therapies, which will represent a clinical and social benefit for these allergic diseases

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The role of regulatory T cells in the acquisition of tolerance to food allergens in children.

Food allergy is a pathological immune reaction that identifies certain harmless food proteins, usually tolerated by the majority of the people, as a threat. The prevalence of these food allergies is increasing worldwide and currently affects 8% of children. Exacerbated reactions to milk, egg and peanut are the most frequent in the pediatric population. It is well known that allergic diseases are a type 2 T-helper (Th2) immune response, characterized by the elevated production of IgE antibodies. However, little is known about the immune mechanisms responsible for the development of clinical tolerance toward food allergens. Recent studies have suggested the key role of regulatory T cells (Tregs) in controlling allergic inflammation. In this review, we discuss the importance of Tregs in the pathogenesis of food allergy and the acquisition of oral tolerance in children. Further investigation in this area will be crucial for the identification of predictive markers and the development of new therapies, which will represent a clinical and social benefit for these allergic diseases.

[Respiratory infections in Emergencies]. / Infecciones respiratorias en Urgencias.

Respiratory infections account for 63.8% of infections met. Of which a quarter are lower respiratory tract: acute bronchitis, exacerbation of COPD or bronchiectasis and pneumonia. Acute bronchitis usually of viral etiology and in immunocompetent patients without comorbidity treatment is symptomatic with analgesics and anti-inflammatories. The main cause of exacerbation of COPD is the respiratory infection. The indication of empirical antibiotic choice and it is based on clinical criteria, the severity of the underlying disease, the severity of the exacerbation and the presence of risk factors for infection with Pseudomonas aeruginosa. The community-acquired pneumonia (CAP) is the leading cause of death by infection. The use of prognostic severity scales (PSI or CURB-65) is recommended for deciding where treatment is started, the tests to be performed for the etiological diagnosis and the recommended empirical antibiotic therapy. Patients with Healthcare Associated Pneumonia (HCAP) and nosocomial pneumonia (NP) have a higher risk of infection by multiresistant microorganisms (MMR) and increased morbidity and mortality. It requires specific empirical treatment depending on the severity of disease and risk factors for infection MMR.

Potential of Ni(II)-NTA-modified poly(ethylene imine) glycopolymers as carrier system for future dendritic cell-based immunotherapy.

Dendritic cells (DCs) play a crucial role in the development of cell-mediated immunotherapy due to their ability to induce and maintain strong immune responses. In our study, we evaluated a biocompatible Ni(II)-NTA-modified poly(ethylene imine) dendritic glycopolymer (Ni(II)-NTA-DG) as new carrier system to increase the antigen uptake into iDCs for future DC-based immunotherapy. Ni(II)-NTA-DG led to an increase in His6-Gp160 uptake in monocytes and iDCs, where His6-Gp160 is localized in the early endosomal and lysosomal compartments. Ni(II)-NTA-DG and the formed polyplexes induced an activation of iDCs, showing an increasing expression of costimulatory molecules CD86, CD80, and proinflammatory cytokines IL-6 and IL-8. Beside no influencing effect of Ni(II)-NTA-DG and polyplexes on the maturation of antigen-bearing DCs, the mature peptide bearing DCs remained their ability to migrate along a gradient of CCR7 ligands. Thus, Ni(II)-NTA-DG with advancing biological properties is a promising carrier system for the future application in DC-based immunotherapy.

Glycodendrimers as new tools in the search for effective anti-HIV DC-based immunotherapies.

Dendritic cells (DC), which play a major role in development of cell-mediated immunity, represent opportunities to develop novel anti-HIV vaccines. Dendrimers have been proposed as new carriers to ameliorate DC antigen loading and in this way, we have determined the potential use of maltose decorated neutrally and positively charged G4 glycodendrimers. Thus, immunostimulatory properties of these glycodendrimers on human DC were evaluated in the context of HIV infection. We have demonstrated that DC treated with glycodendrimers were fully functional with respect to viability, maturation and HIV-derived antigens uptake. Nevertheless, iDC and mDC phenotypes as well as mDC functions such as migration ability and cytokines profile production were changed. Our results showed the potential carrier properties of glycodendrimers to activate the immune system by the way of DC stimulation. This is the first study for exploring the use of maltose-functionalized dendrimers-peptides complexes as a potential DC-based vaccine candidate. FROM THE CLINICAL EDITOR: In this paper, maltose-functionalized dendrimer-peptide complexes are demonstrated to activate the immune system by way of dendritic cell (DC) stimulation. DC vaccination using this methodology may be applicable to a variety of conditions, including infections and potentially cancer.

Carbosilane dendrimer nanotechnology outlines of the broad HIV blocker profile.

Researchers have been working hard for more than 20 years to develop safe and effective microbicides to empower women to better control their own sexual life and to protect themselves against HIV and other sexually transmitted infections (STIs). Microbicide classes include moderately specific macromolecular anionic polymers that block HIV and other STIs, and HIV specific drugs that inhibit viral entry and reverse transcription. Based on innovative nanotechnology design, we showed a novel water-soluble anionic carbosilane dendrimer (2G-S16) as a propitious molecule against HIV-infection. A state-of-the-art research was accomplished that focused on biomedical cutting-edge techniques such as in vitro and in vivo cytotoxicity assays performed on female rabbit genital tracts, simulate in vitro model of vaginal epithelium in order to evaluate HIV transmission blockade through the monolayer, complete gene expression profiling experiment to study deregulated genes after 2G-S16 exposition, molecular dynamics simulation of 2G-S16 molecule against principal proteins of HIV particles and pro- and anti-inflammatory cytokine profile study. Therefore, a high-throughput study and detailed analysis of the results were achieved in this article. We provided promising outcomes to encourage 2G-S16 as a hopeful microbicide.

Airport smoking rooms don't work.

OBJECTIVES: To document tobacco industry involvement in thwarting enactment of a smoke-free airport policy at Lambert-St Louis International Airport (Lambert Airport) in the 1990s; and to test whether smoking rooms at Lambert Airport protect non-smokers from exposure to secondhand tobacco smoke (SHS) in adjacent non-smoking areas. METHODS: Tobacco industry document websites were searched for previously secret documents relating to efforts to maintain smoking in Lambert Airport. Testing of SHS contamination in non-smoking areas adjacent to a designated smoking room was conducted at Lambert Airport in 1997-98 and again in 2002. A 1998 comparative test was also performed inside nominally smoke-free Seattle-Tacoma International Airport (Sea-Tac Airport). Tests were performed using either static or active nicotine monitors. RESULTS: Industry documents show that the tobacco industry promoted the construction of designated smoking rooms as a way to sidetrack efforts to make Lambert Airport entirely non-smoking. Nicotine vapour air monitoring in a non-smoking area of the airport, adjacent to a smoking room located in Terminal C, reveals elevated levels of ambient nicotine vapour in excess of what would be expected in a completely non-smoking environment. CONCLUSIONS: This study shows that airport smoking rooms expose non-smokers in adjacent non-smoking areas to a significant concentration of nicotine vapour from SHS.

Extensively deleted simian immunodeficiency virus (SIV) DNA in macaques inoculated with supercoiled plasmid DNA encoding full-length SIVmac239.

Using long-distance DNA PCR, we prospectively followed rhesus monkeys that had been inoculated intramuscularly with supercoiled plasmid DNA encoding intact simian immunodeficiency virus (SIV). From 4 to 10 weeks postinoculation onward, we detected extensively deleted proviral genomes along with full-length viral genomes in peripheral blood mononuclear cells (PBMC) in adult macaques. During their chronic asymptomatic phase of infection, the frequency of deleted proviral genomes was similar in PBMC and lymph nodes. The latter, however, harbored significantly more full-length proviral DNA than PBMC, consistent with the lack of effective antiviral cytotoxic T-cell activity in lymph nodes described by others during human immunodeficiency virus infection. After the macaques progressed to AIDS, full-length proviral DNA became equally abundant in lymph nodes and in PBMC. We have demonstrated that although a single molecular species of proviral DNA was inoculated, genomic diversity was detected within a short time, thus confirming the genetic instability of the SIV genome in vivo.

Production of HIV-1 by resting memory T lymphocytes.

BACKGROUND: The persistence of HIV-1 within resting memory CD4 T cells constitutes a major obstacle in the control of HIV-1 infection. OBJECTIVE: To examine the expression of HIV-1 in resting memory CD4 T cells, using an in-vitro model. DESIGN AND METHODS: Phytohaemagglutinin-activated peripheral blood mononuclear cells were challenged with T cell-tropic and macrophage-tropic HIV-1 clones, and with a replication-incompetent and non-cytotoxic HIV-1-derived vector (HDV) pseudotyped by the vesicular stomatitis virus glycoprotein G. To obtain resting memory CD4 T cells containing HIV-1 provirus, residual CD25(+), CD69(+) and HLA-DR(+) cells were immunodepleted after a 3 week cultivation period. RESULTS: In spite of the resting phenotype, the majority of provirus-harbouring T cells expressed HIV-1 genomes and produced infectious virus into cell-free supernatant. The expression of HDV dropped by only 30% during the return of activated HDV-challenged cells into the quiescent phase. Although resting memory T cells generated in vitro expressed HIV-1 and HDV genome when infected during the course of the preceding T cell activation, they were resistant to HIV-1 and HDV challenge de novo. The infected culture of resting memory T cells showed a higher resistance to the cytotoxic effects of HIV-1 in comparison with the same cultures after reactivation by phytohaemagglutinin. CONCLUSION: The majority of resting memory T cells infected during the course of a preceding cell activation produces virus persistently, without establishing a true HIV-1 latency. The described system could be used as a model for testing new drugs able to control residual HIV-1 replication in resting memory T cells.

[Management of pain in the home]. / Approche de la douleur à domicile.

Since patients treated with analgesics at home exist in ever-increasing numbers, and nurses are convinced of the efficacity of the treatment of pain, we are confronted with an urgent need for competent training. This is why, for a little over a year now, nurses have benefitted from theoretical and practical aids, allowing them to work more effectively, be it on the educative, therapeutic, technical and human level, so that patients benefit from a better quality of life and die in comfort and dignity.