CD80, but not CD86 were up-regulated on the spleen-derived dendritic cells from OVA-sensitized and challenged BALB/c mice
ABSTRACT Allergen-specific CD4+ T-helper (Th) 2 cells are involved in the induction and effector phase of allergic asthma. It is well established that T cells activation requires interaction of T cell receptor (TCR) and MHC-peptide complex, as well as costimulatory signal delivered by antigen presenting cells (APCs). There is increasing evidence that CD80 (B7.1) and CD86 (B7.2), as the most important costimulatory molecules, are involved in the allergic immune responses. In the present study, we investigated the CD80 and CD86 expression of spleen-derived dendritic cells (DCs) in a murine model of allergic asthma. We first established a murine model of ovalbumin (OVA)-allergic asthma that showed unique histological characteristic of allergic inflammation in the lung, high serum OVA-specific IgE level, high numbers of eosinophils in the bronchoalveolar lavage (BAL) and high production of Type 2 cytokines in the splenic T cells. In this model, we found that CD80 were significantly upregulated on the spleen-derived DCs from OVA-sensitized and challenged mice compared with that from PBS-treated or non-treated mice, while CD86 is not different among three groups. Furthermore, we demonstrated that Th2 immune responses were elicited by these DCs with high expression of CD80, even to nai;ve T cells from non-treated mice. Our results suggest that DCs in the spleen of allergic mice, via upregulation of CD80 might play a pivotal role in the maintenance and amplification of allergic immune response, namely Th2 immune response.
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ABSTRACT: Background: Allergen-induced imbalance of specific T regulatory (Treg) cells and T helper 2 cells plays a decisive role in the development of immune response against allergens. Objective: To evaluate effects and potential mechanisms of DNA vaccine containing ovalbumin (OVA) and Fc fusion on allergic airway inflammation.
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ABSTRACT: Experimental mouse models of allergic asthma established almost 10 years ago offered new opportunities to study disease pathogenesis and to develop new therapeutics. These models focused on the factors governing the allergic immune response, on modeling clinical behavior of allergic asthma, and led to insights into pulmonary pathophysiology. Although mouse models rarely completely reproduce all the features of human disease, after sensitization and respiratory tract challenges with antigen, wild-type mice develop a clinical syndrome that closely resembles allergic asthma, characterized by eosinophilic lung inflammation, airway hyperresponsiveness (AHR), increased IgE, mucus hypersecretion, and eventually, airway remodeling. There are, however, differences between mouse and human physiology that threaten to limit the value of mouse models. Three examples of such differences relate to both clinical manifestations of disease and underlying pathogenesis. First, in contrast to patients who have increased methacholine-induced AHR even when they are symptom-free, mice exhibit only transient methacholine-induced AHR following allergen exposure. Second, chronic allergen exposure in patients leads to chronic allergic asthma, whereas repeated exposures in sensitized mice causes suppression of disease. Third, IgE and mast cells, in humans, mediate early- and late-phase allergic responses, though both are unnecessary for the generation of allergic asthma in mice. Taken together, these observations suggest that mouse models of allergic asthma are not exact replicas of human disease and thus, question the validity of these models. However, observations from mouse models of allergic asthma support many existing paradigms, although some novel discoveries in mice have yet to be verified in patients. This review presents an overview of the clinical aspects of disease in mouse models of allergic asthma emphasizing (1). the factors influencing the pathophysiological responses during the initiation and perpetuation of disease, (2). the utility of mouse models for studying clinical manifestations of disease, and (3). the applicability of mouse models for testing new treatments for allergic asthma.International Archives of Allergy and Immunology 02/2004; 133(1):84-100. DOI:10.1159/000076131 · 2.43 Impact Factor
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ABSTRACT: This study tested the hypotheses that chronic allergic inflammation induces not only bronchial but also lung parenchyma remodeling, and that these histologic changes are associated with concurrent changes in respiratory mechanics. For this purpose, airway and lung parenchyma remodeling were evaluated by quantitative analysis of collagen and elastin, immunohistochemistry (smooth-muscle actin expression, eosinophil, and dendritic cell densities), and electron microscopy. In vivo (airway resistance, viscoelastic pressure, and static elastance) and in vitro (tissue elastance, resistance, and hysteresivity) respiratory mechanics were also analyzed. BALB/c mice were sensitized with ovalbumin and exposed to repeated ovalbumin challenges. A marked eosinophilic infiltration was seen in lung parenchyma and in large and distal airways. Neutrophils, lymphocytes, and dendritic cells also infiltrated the lungs. There was subepithelial fibrosis, myocyte hypertrophy and hyperplasia, elastic fiber fragmentation, and increased numbers of myofibroblasts in airways and lung parenchyma. Collagen fiber content was increased in the alveolar walls. The volume proportion of smooth muscle-specific actin was augmented in distal airways and alveolar duct walls. Airway resistance, viscoelastic pressure, static elastance, and tissue elastance and resistance were significantly increased. In conclusion, prolonged allergen exposure induced remodeling not only of the airway wall but also of the lung parenchyma, leading to in vivo and in vitro mechanical changes.American Journal of Respiratory and Critical Care Medicine 05/2005; 171(8):829-37. DOI:10.1164/rccm.200408-997OC · 11.99 Impact Factor