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Tolerogenic dendritic cells derived from donors with natural rubber latex allergy modulate allergen-specific T-cell responses and IgE production.

ABSTRACT: Natural rubber latex (NRL; Hevea brasiliensis) allergy is an IgE-mediated reaction to latex proteins. When latex glove exposure is the main sensitizing agent, Hev b 5 is one of the major allergens. Dendritic cells (DC), the main antigen presenting cells, modulated with pharmacological agents can restore tolerance in several experimental models, including allergy. In the current study, we aimed to generate DC with tolerogenic properties from NRL-allergic patients and evaluate their ability to modulate allergen-specific T and B cell responses. Here we show that dexamethasone-treated DC (dxDC) differentiated into a subset of DC, characterized by low expression of MHC class II, CD40, CD80, CD86 and CD83 molecules. Compared with LPS-matured DC, dxDC secreted lower IL-12 and higher IL-10 after CD40L activation, and induced lower alloantigenic T cell proliferation. We also show that dxDC pulsed with the dominant Hev b 5 T-cell epitope peptide, Hev b 5(46-65), inhibited both proliferation of Hev b 5-specific T-cell lines and the production of Hev b 5-specific IgE. Additionally, dxDC induced a subpopulation of IL-10-producing regulatory T cells that suppressed proliferation of Hev b 5-primed T cells. In conclusion, dxDC generated from NRL-allergic patients can modulate allergen-specific T-cell responses and IgE production, supporting their potential use in allergen-specific immunotherapy.

SUBMITTER: Escobar A

PROVIDER: S-EPMC3899084 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Tolerogenic dendritic cells derived from donors with natural rubber latex allergy modulate allergen-specific T-cell responses and IgE production.

Escobar Alejandro A Aguirre Adam A Guzmán María Antonieta MA González Rodrigo R Catalán Diego D Acuña-Castillo Claudio C Larrondo Milton M López Mercedes M Pesce Barbara B Rolland Jennifer J O'Hehir Robyn R Aguillón Juan Carlos JC

PloS one 20140122 1

Natural rubber latex (NRL; Hevea brasiliensis) allergy is an IgE-mediated reaction to latex proteins. When latex glove exposure is the main sensitizing agent, Hev b 5 is one of the major allergens. Dendritic cells (DC), the main antigen presenting cells, modulated with pharmacological agents can restore tolerance in several experimental models, including allergy. In the current study, we aimed to generate DC with tolerogenic properties from NRL-allergic patients and evaluate their ability to mod ...[more]

PMID: 24465795

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Project description:Although natural rubber was regarded as biodegradable, the degradation is a time-consuming process that could take weeks or months for any degradation or substantial weight loss to be observable, resulting in the need for novel processes/methods to accelerate the rubber degradation. As a result, this work investigated the potential utilization of chitosan (CS) as a biodegradation enhancer for radiation-vulcanized natural rubber latex (R-VNRL) and hybrid radiation and peroxide-vulcanized natural rubber latex (RP-VNRL) composites, with varying CS contents (0, 2, 4, or 6 phr). The R-VNRL samples were prepared using 15 kGy gamma irradiation, while the RP-VNRL samples were prepared using a combination of 0.1 phr tert-butyl hydroperoxide (t-BHPO) and 10 kGy gamma irradiation. The properties investigated were biodegradability in the soil and the morphological, chemical, mechanical, and physical properties, both before and after undergoing thermal aging. The results indicated that the biodegradability of both the R-VNRL and RP-VNRL composites was enhanced with the addition of CS, as evidenced by increases in the percentage weight loss (% weight loss) after being buried in soil for 8 weeks from 6.5 ± 0.1% and 6.4 ± 0.1% in a pristine R-VNRL and RP-VNRL samples, respectively, to 10.5 ± 0.1% and 10.2 ± 0.1% in 6-pph CS/R-VNRL and 6-pph CS/RP-VNRL composites, respectively, indicating the biodegradation enhancement of approximately 60%. In addition, the results revealed that the addition of CS could increase the value of tensile modulus by 119%, while decrease the values of tensile strength and elongation at break by 50% and 43%, respectively, in the specimens containing 6-phr CS. In terms of the color appearances, the samples were lighter and yellower after the addition of CS, as evidenced by the noticeably increased L* and b* values, based on the CIE L*a*b* color space system. Furthermore, the investigation into the effects of thermal aging showed that the overall tensile properties for both curing systems were reduced, while varying degrees of color change were observed, with the pristine R-VNRL and RP-VNRL samples having more pronounced degradation/changes for both properties. In conclusion, the overall results suggested that CS had great potential to be applied as a bio-filler in R-VNRL and RP-VNRL composites to effectively promote the biodegradability, environmental friendliness, and resistance to thermal degradation of the composites.

Project description:Cat allergy is a major trigger factor for respiratory reactions (asthma and rhinitis) in patients with immunoglobulin E (IgE) sensitization. In this study, we used a comprehensive panel of purified cat allergen molecules (rFel d 1, nFel d 2, rFel d 3, rFel d 4, rFel d 7, and rFel d 8) that were obtained by recombinant expression in Escherichia coli or by purification as natural proteins to study possible associations with different phenotypes of cat allergy (i.e., rhinitis, conjunctivitis, asthma, and dermatitis) by analyzing molecular IgE recognition profiles in a representative cohort of clinically well-characterized adult cat allergic subjects (n = 84). IgE levels specific to each of the allergen molecules and to natural cat allergen extract were quantified by ImmunoCAP measurements. Cumulative IgE levels specific to the cat allergen molecules correlated significantly with IgE levels specific to the cat allergen extract, indicating that the panel of allergen molecules resembled IgE epitopes of the natural allergen source. rFel d 1 represented the major cat allergen, which was recognized by 97.2% of cat allergic patients; however, rFel d 3, rFel d 4, and rFel d 7 each showed IgE reactivity in more than 50% of cat allergic patients, indicating the importance of additional allergens in cat allergy. Patients with cat-related skin symptoms showed a trend toward higher IgE levels and/or frequencies of sensitization to each of the tested allergen molecules compared with patients suffering only from rhinitis or asthma, while there were no such differences between patients with rhinitis and asthma. The IgE levels specific to allergen molecules, the IgE levels specific to cat allergen extract, and the IgE levels specific to rFel d 1 were significantly higher in patients with four different symptoms compared with patients with 1-2 symptoms. This difference was more pronounced for the sum of IgE levels specific to the allergen molecules and to cat extract than for IgE levels specific for rFel d 1 alone. Our study indicates that, in addition to rFel d 1, rFel d 3, rFel d 4, and rFel d 7 must be considered as important cat allergens. Furthermore, the cumulative sum of IgE levels specific to cat allergen molecules seems to be a biomarker for identifying patients with complex phenotypes of cat allergy. These findings are important for the diagnosis of IgE sensitization to cats and for the design of allergen-specific immunotherapies for the treatment and prevention of cat allergy.

Dataset Information

Tolerogenic dendritic cells derived from donors with natural rubber latex allergy modulate allergen-specific T-cell responses and IgE production.

Publications

Tolerogenic dendritic cells derived from donors with natural rubber latex allergy modulate allergen-specific T-cell responses and IgE production.

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