CD80, but not CD86 were up-regulated on the spleen-derived dendritic cells from OVA-sensitized and challenged BALB/c mice

Third Military Medical University, Ch’ung-ch’ing-shih, Chongqing Shi, China
Immunology Letters (Impact Factor: 2.51). 11/2003; 89(1):31-8. DOI: 10.1016/S0165-2478(03)00107-X
Source: PubMed


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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    • "Spleen DCs were enriched as described previously [7]. Briefly, after the spleen was disrupted, the cells were centrifuged at 1300 rpm for 5 min, resuspended in RPMI 1640 medium supplemented with 10% heat-activated fetal calf serum, 2 mmol/l L-glutamine, 1 mmol/l pyruvate, 50 μmol/l mercaptoethanol, 100 U/ml penicillin, and 100 μg/ml streptomycin, and then incubated in plastic cell cultures plates for 2 h at 37°C in a 5% CO2 atmosphere. "
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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.
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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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    No preview · Article · Feb 2004 · International Archives of Allergy and Immunology
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