Home About us Contact
|
Home About us Contact | ||
|
|
||
Allergic Immune Responses (allergic + immune_response)
Selected AbstractsHuman dendritic cells transfected with allergen-DNA stimulate specific immunoglobulin G4 but not specific immunoglobulin E production of autologous B cells from atopic individuals in vitroIMMUNOLOGY, Issue 2 2007Bettina König Summary Atopic/allergic diseases are characterized by T helper 2 (Th2)-dominated immune responses resulting in immunoglobulin E (IgE) production. DNA-based immunotherapies have been shown to shift the immune response towards Th1 in animal models. In further studies we showed that human dendritic cells (DC) transfected with allergen-DNA are able to stimulate autologous CD4+ T cells from atopic individuals to produce Th1 instead of Th2 cytokines and to activate interferon-, (IFN-,)-producing CD8+ T cells. The aim of this study was to analyse whether DC transfected with allergen-DNA are also able to influence immunoglobulin production of B cells from atopic donors. For this purpose, human monocyte-derived DC from grass-pollen allergic donors were transfected with an adenovirus encoding the allergen Phleum pratense 1 and cocultured with B cells, autologous CD4+ T cells, and CD40 ligand-transfected L-cells. B cells receiving help from CD4+ T cells stimulated with allergen-transfected dendritic cells produced more allergen-specific IgG4 compared to stimulation with allergen protein pulsed DC or medium, while total IgG4 production was not affected. In contrast, specific IgE production was not enhanced by stimulation with allergen-DNA transfected DC compared to medium and inhibited compared to allergen protein-pulsed DC with similar effects on total IgE production in vitro. Allergen-DNA transfected dendritic cells are able to direct the human allergic immune response from Th2-dominance towards Th1 and Tc1 also resulting in decreased IgE and increased IgG4 production. [source] Birth order, atopy, and symptoms of allergy and asthma among inner-city children attending Head Start in New York CityCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2008M. S. Perzanowski Summary Background In past research, children with older siblings were more likely than others to wheeze at age 2 years, but less likely by age 6 years. Higher infection transmission and a down-regulated allergic immune response as a result of these infections, respectively, were suggested as the causes. However, in a study of children aged 0,3 years in a low-income urban community in New York City, USA, with high asthma prevalence, we observed no birth-order effect. Objective To evaluate the association between birth order and atopy and respiratory symptoms in 4-year-old children attending Head Start programs in NYC. Methods Respiratory symptoms were assessed by questionnaire for 1005 children (mean age 4.0 years) living in high asthma prevalence neighbourhoods. Serum was collected from a subgroup of the children (n=494) and specific IgE responses to dust mite, cockroach, mouse, and cat allergens were measured. Results Prevalence of specific IgE (0.35 IU/mL) did not differ significantly among first (35%), second (35%), and later-born children (28%) (P=0.23). Increasing birth order was associated with increasing prevalence of respiratory symptoms in the prior year, including wheeze (first 20%, second 27%, third or later 35%; P<0.001), being awakened at night by cough (28%, 33%, 38%; P=0.005), emergency department visits (14%, 17%, 21%; P=0.02) and hospitalizations for difficulty breathing (6.1%, 6.6%, 10%; P=0.04). The associations of birth order with respiratory symptoms were statistically significant only for the non-seroatopic children and those without an asthmatic parent. Conclusions Non-seroatopic children with older siblings were more likely than those without older siblings to have respiratory symptoms at age 4 years. Although the stability of these associations over time remains to be determined, the differences in findings between this study and our previous NYC birth cohort study suggest that patterns of asthma development may vary even among low-income populations within the same city. [source] Enhanced interleukin-4 production in CD4+ T cells and elevated immunoglobulin E levels in antigen-primed mice by bisphenol A and nonylphenol, endocrine disruptors: involvement of nuclear factor-AT and Ca2+IMMUNOLOGY, Issue 1 2003Mee H. Lee Summary Bisphenol A (BPA) and p -nonylphenol (NP) are representative endocrine disruptors (EDs) that may have adverse effects on human health. The influence of these compounds on allergic immune responses remains unclear. In this study, we have examined the effects of BPA and NP on production of interleukin-4 (IL-4), a pro-inflammatory cytokine closely associated with allergic immune responses. Both BPA and NP significantly enhanced IL-4 production in keyhole limpet haemocyanin (KLH)-primed CD4+ T cells in a concentration-dependent manner. Treatment with BPA or NP in vivo resulted in significant increase of IL-4 production in CD4+ T cells and of antigen-specific immunoglobulin E (IgE) levels in the sera of KLH-primed mice. Furthermore, BPA and NP enhanced the activation of IL-4 gene promoter in EL4 T cells transiently transfected with IL-4 promoter/reporter constructs, and the enhancing effect mapped to a region in the IL-4 promoter containing binding sites for nuclear factor (NF)-AT. Activation of T lymphocytes by phorbol 12-myristate 13-acetate/ionomycin resulted in markedly enhanced binding activities to the NF-AT site, which significantly increased upon addition of BPA or NP, as demonstrated by the electrophoretic mobility shift assay, indicating that the transcription factor NF-AT was involved in the enhancing effect of BPA and NP on IL-4 production. The enhancement of IL-4 production by BPA or NP was significantly reduced by nitrendipine, a blocker of Ca2+ influx, and by FK506, a calcineurin inhibitor. FK506 inhibited the NF-AT,DNA binding activity and IL-4 gene promoter activity enhanced by BPA or NP. These results represent the first report describing possible enhancement of allergic response by EDs through increasing IL-4 production in CD4+ T cells and antigen-specific IgE levels in the sera via the stimulation of Ca2+/calcineurin-dependent NF-AT activation. [source] A novel study design to investigate the early-life origins of asthma in children (SAGE study)ALLERGY, Issue 8 2009A. L. Kozyrskyj This is a description of the Study of Asthma, Genes and the Environment (SAGE), a novel birth cohort created from provincial healthcare administrative records. It is a general population-based cohort, composed of children at high and low risk for asthma, living in urban and rural environments in Manitoba, Canada. The SAGE study captures the complete longitudinal healthcare records of children born in 1995 and contains detailed information on early-life exposures, such as antibiotic utilization and immunization, in relationship to the development of asthma. Nested within the birth cohort is a case-control study, which was created to collect information on home environmental exposures from detailed surveys and home dust sampling, to confirm asthma status in children and use this data to validate healthcare database measures of asthma, to determine differences in immune system responsiveness to innate and adaptive immune stimuli in asthma, to genotype children for genes likely associated with the development of asthma and to study the epigenetic regulation of pre-established protective vs allergic immune responses. The SAGE study is a multidisciplinary collaboration of researchers from pediatric allergy, population health, immunology, and genetic and environmental epidemiology. As such, it serves as a fertile, interdisciplinary training ground for graduate students, and postdoctoral and clinician fellows. [source] Prolonged antigen-exposure with carbohydrate particle based vaccination prevents allergic immune responses in sensitized miceALLERGY, Issue 6 2009S. Thunberg Background:, Defined particles carrying tightly bound allergens at high density have been suggested as alternatives in allergy vaccination. Carbohydrate based particles (CBP), sized 2 ,m, provide a platform for covalent coupling of allergens. Objective:, To investigate the mechanisms of antigen presentation by CBP, as well as cellular and humoral responses after vaccination with the major cat allergen Fel d 1, covalently coupled to CBP. Methods:, Mice (n = 10/group) were subcutaneously vaccinated with CBP-rFel d 1, CBP or phosphate buffer saline (PBS) before sensitization with rFel d 1 and challenged with cat dander extract. Fluorescent and 75Se-radiolabeled tracking of allergens and particles were performed with flow cytometry and whole-body autoradiography. Humoral, cellular and regulatory immune responses were analyzed by ELISA and flow cytometry. Cytokines were measured in bronchoalveolar lavage fluid and splenocyte cultures. Results:, CBP-rFel d 1 prevented induction of airway inflammation and induced allergen-specific T-cell anergy. CBP-rFel d 1 also induced rapid IgM and IgG1-responses compared with soluble rFel d 1. Particles were phagocytosed by antigen-presenting cells and transported to draining lymph nodes and spleen. Moreover, antigen coupled to CBP remained longer at the injection site compared with alum. Conclusions:, Covalent coupling of rFel d 1 to CBP induces rapid antibody production, prevents induction of allergic immune responses and systemic allergen spreading. Thus, CBP comprise several attractive adjuvant features for use in allergy vaccination. Clinical Implications:, Prolonged allergen exposure through covalent coupling to particles suitable for phagocytosis, provides an adjuvant for safer and efficient allergy vaccination. [source] Inhibition of human allergic T-helper type 2 immune responses by induced regulatory T cells requires the combination of interleukin-10-treated dendritic cells and transforming growth factor-, for their inductionCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2006I Bellinghausen Summary Background In grass pollen-allergic individuals, T cell anergy can be induced by IL-10-treated dendritic cells (IL-10-DC) resulting in the suppression of T helper type 1 (Th1) as well as Th2 cells. This study was performed to analyse whether such IL-10-DC-treated T cells are able to act as regulatory T cells (Treg) suppressing the function of other T cells in the periphery. As transforming growth factor (TGF)-, is also a potential inducer of Treg, we additionally analysed the inhibitory capacity of TGF-,-treated T cells in this system. Materials and Methods Freshly isolated CD4+ or CD4+CD25, T cells from grass pollen-allergic donors were stimulated with autologous mature monocyte-derived allergen-pulsed DC in the presence or absence of T cells previously cultured with IL-10-DC- and/or TGF-,. Results Anergic T cells induced by allergen-pulsed IL-10-treated DC or allergen-pulsed DC and TGF-, enhanced IL-10 production and strongly inhibited IFN-, production of freshly prepared peripheral CD4+ or CD4+CD25, T cells while proliferation and Th2 cytokine production were only slightly reduced. The combination of allergen-pulsed IL-10-treated DC and TGF-, had an additional effect leading to a significant suppression also of Th2 cytokine production and proliferation. Suppression was not antigen-specific and was mainly mediated by cell-to-cell contact and by the molecule-programmed death-1 and only partially by CTLA-4, TGF-, and IL-10. Conclusion These data demonstrate that regulatory T cells that also suppress Th2 cytokine production are induced by two signals: TGF-, and IL-10-DC. This is of importance for the regulation of allergic immune responses and might be exploited for future therapeutic strategies for allergic diseases. [source] Surfactant protein D deficiency influences allergic immune responsesCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2004B. Schaub Summary Background The collectin surfactant protein D (SP-D) confers protection against pulmonary infection and inflammation. Recent data suggest a role for SP-D in the modulation of allergic inflammation. Objective The aim of this study is to characterize the immune responses of SP-D-deficient (SP-D,/,) mice in a kinetic model of allergic inflammation. We determined whether allergic parameters were enhanced in SP-D,/, mice in vivo. Further, we examined whether functional immune responses in vitro such as lymphocyte proliferation (LP) and cytokine production were modulated in the absence of SP-D. Methods In vivo, wild-type (WT) and SP-D,/, mice were sensitized and challenged with the allergen ovalbumin (OVA) and assessed for allergic parameters (bronchoalveolar lavage (BAL) eosinophils, IL-13 production, pulmonary IFN-,, IL-10 expression) at early time points (1 and 3 days of challenge) in comparison with late time points (7 days of challenge). In vitro, spleen cells from WT and SP-D,/, mice were stimulated with the mitogen concanavalin A (ConA) and lipid A (LpA) and analysed for LP, IL-13 and IFN-, production. Toll-like receptor 4 (TLR4), ligand for LpA, was assessed by mRNA expression and immunohistochemistry in vivo. Results Following allergen exposure in vivo, SP-D,/, mice expressed higher BAL eosinophils and IL-13 concentrations and lower IFN-, expression at early time points compared with WT mice. IL-10 expression was increased at early time points in SP-D,/, compared with WT mice. Allergen-induced TLR4 expression was increased in WT, but not in SP-D,/, mice. After stimulation with LpA and ConA in vitro LP was increased and IFN-, concentration was decreased in SP-D,/, mice. Conclusion SP-D may be critical for the modulation of early stages of allergic inflammation in vivo. [source] DNA VACCINES AND ALLERGIC DISEASESCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2006Kaw Yan Chua SUMMARY 1Allergic diseases are characterized by inappropriate immune responses to common environmental antigens. The prevalence of these diseases has been increasing worldwide for reasons that are not exactly clear. 2Current treatment is largely symptomatic. Because the initial observation that simple plasmid DNA injections resulted in in vivo protein expression and induction of adaptive immune responses to the encoded antigen, the potential of modifying the allergic immune responses by DNA vaccination so as to treat and prevent these diseases has been explored extensively. 3In the present paper we review preclinical studies using animal models of allergic diseases, with an emphasis on DNA vaccine design, for house dust mite allergens-related allergic asthma. [source] | ||||||||||