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: 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. To evaluate effects and potential mechanisms of DNA vaccine containing ovalbumin (OVA) and Fc fusion on allergic airway inflammation. Bronchoalveolar lavage (BAL) levels of inflammatory mediators and leukocyte infiltration, expression of CD11c+CD80+ and CD11c+CD86+ co-stimulatory molecules in spleen dendritic cells (DCs), circulating CD4+ and CD8+ T cells, Foxp3+ in spleen CD4+ T cells and spleen CD4+ T cells were measured in OVA-sensitized and challenged animals pretreated with pcDNA, OVA-pcDNA, Fc-pcDNA, and OVA-Fc-pcDNA. OVA-Sensitized and challenged mice developed airway inflammation and Th2 responses, and decreased the proliferation of peripheral CD4+and CD8+ T cells and the number of spleen Foxp3+ Treg. Those changes with increased INF-gamma production and reduced OVA-specific IgE production were protected by the pretreatment with OVA-Fc-pcDNA. DNA vaccine encoding both Fc and OVA showed more effective than DNA vaccine encoding Fc or OVA alone, through the balance of DCs and Treg.Genetic Vaccines and Therapy 03/2010; 8:2. · 2.10 Impact Factor
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ABSTRACT: Protein tyrosine phosphatase 1B (PTP-1B) is a ubiquitously expressed cytosolic phosphatase with the ability to dephosphorylate JAK2 and TYK2, and thereby down-regulate cytokine receptor signaling. Furthermore, PTP-1B levels are up-regulated in certain chronic myelogenous leukemia patients, which points to a potential role for PTP-1B in myeloid development. The results presented here show that the absence of PTP-1B affects murine myelopoiesis by modifying the ratio of monocytes to granulocytes in vivo. This bias toward monocytic development is at least in part due to a decreased threshold of response to CSF-1, because the PTP-1B -/- bone marrow presents no abnormalities at the granulocyte-monocyte progenitor level but produces significantly more monocytic colonies in the presence of CSF-1. This phenomenon is not due to an increase in receptor levels but rather to enhanced phosphorylation of the activation loop tyrosine. PTP-1B -/- cells display increased inflammatory activity in vitro and in vivo through the constitutive up-regulation of activation markers as well as increased sensitivity to endotoxin. Collectively, our data indicate that PTP-1B is an important modulator of myeloid differentiation and macrophage activation in vivo and provide a demonstration of a physiological role for PTP-1B in immune regulation.Proceedings of the National Academy of Sciences 03/2006; 103(8):2776-81. · 9.74 Impact Factor
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ABSTRACT: Vaccination with allergen-encoding DNA has been proposed as having potential for allergen-specific immunotherapy. In this study, we examine the therapeutic effect of allergen-encoding DNA vaccination directly to dendritic cells (DCs) on allergen-induced allergic airway inflammation in a mouse model and explore potential mechanism. Ovalbumin (OVA)-sensitized and challenged mice were immunized with DNA vaccine and received bronchoalveolar lavage (BAL) 1 day after the last challenge, to measure BAL levels of interleukin (IL)-4, IL-5, interferon (IFN)-gamma and differential cell count. Pulmonary DCs and Spleen DCs were purified and sorted according to the expression of CD(11c) (+)CD(80) (+) and CD(11c) (+)CD(86) (+) co-stimulatory molecules. Our data demonstrated that DNA vaccine therapy with OVA-Fc-pcDNA(3.1) significantly prevented OVA-increased levels of IL-4, IL-5 and the percentage of eosinophils and OVA-decreased level of IFN-gamma. OVA-Fc-pcDNA(3.1)-treated mice had less severity of airway inflammation, and lower expression of CD(11c) (+)CD(80) (+) and CD(11c) (+)CD(86) (+) on pulmonary DCs, as compared with animals with OVA-pcDNA(3.1,) pcDNA(3.1) and OVA respectively. DNA vaccine encoding both Fc and OVA was shown to be more effective than DNA vaccine encoding OVA alone. Our data indicate that Fc-antigen combination-encoding DNA vaccination has better preventive effects on antigen-induced airway inflammation by regulating DCs, and may be a new alternative therapy for asthma.Clinical & Experimental Immunology 09/2008; 154(1):115-22. · 3.41 Impact Factor