Mice vaccinated with allergen-pulsed myeloid dendritic cells are not protected from developing allergen-induced Th2 responses.

Abstract

BACKGROUND:

Dendritic cells (DC) play a decisive role in the induction of allergen-induced Th1 and Th2 responses. Since the induction of allergen-specific Th1 responses has shown to inhibit allergen-induced Th2-type inflammation, in this study we investigated whether manipulated myeloid-derived DC pulsed with the specific allergen would predominantly induce allergen-specific Th1 responses thereby reducing the development of Th2 responses.

METHODS:

Murine bone marrow (BM)-DC were generated and pulsed with ovalbumin (OVA) and CpG oligodeoxynucleotides (CpG-ODN). Langerhans cells (LC) were also isolated and pulsed in vitro with OVA. Subsequently, mice were vaccinated intravenously with either CpG/OVA-pulsed BM-DC or OVA-pulsed LC, and the protocol to induce OVA-specific Th2 responses using OVA/alum sensitization was initiated. Airway inflammation and OVA-specific serum antibody levels were evaluated 6 days after the intranasal challenge with OVA.

RESULTS:

The application ofCpG/OVA-pulsed BM-DC was unable to reduce airway eosinophilia and inflammation in OVA/alum-immunized mice. OVA-specific IgG1 or IgE serum levels were also not reduced. The experiments using LC pulsed with OVA yielded similar results. However, mice vaccinated with CpG/OVA-pulsed BM-DC had greatly enhanced levels of serum OVA-specific IgG2a, suggesting the induction of allergen-specific Th1 responses in vivo. Moreover, allergen-induced mast cell degranulation was decreased using this approach.

CONCLUSIONS:

Taken together, our results demonstrated that the vaccination with OVA-pulsed BM-DC matured with CpG-ODN or OVA-pulsed LC did not result in a reduction in allergen-specific Th2 responses in a murine model of severe atopic asthma. Other DC-based vaccination strategies should be evaluated in order to prevent the development of allergic disorders.

• Authors: Claudia Milena Trujillo-Vargas, José Robinson Ramirez-Pineda, Alois Palmetshofer, Susanne Grunewald, Heidrun Moll, Christoph Berberich, Klaus Joseph Erb
• Journal: International archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 137 Issue 3 Pg. 219-28 (Jul 2005) ISSN: 1018-2438 [Print] Switzerland
• PMID: 15956790 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2005 S. Karger AG, Basel

Chemical References

• Allergens
• CPG-oligonucleotide
• Cytokines
• Immunoglobulin G
• Oligodeoxyribonucleotides
• Vaccines
• Immunoglobulin E
• Ovalbumin

Topics

• Allergens (administration & dosage, immunology)
• Animals
• Base Sequence
• Cytokines (metabolism)
• Dendritic Cells (immunology)
• Eosinophilia (therapy)
• Female
• Immunoglobulin E (biosynthesis, blood)
• Immunoglobulin G (biosynthesis, blood)
• Mice
• Molecular Sequence Data
• Myeloid Cells (immunology)
• Oligodeoxyribonucleotides (administration & dosage, immunology)
• Ovalbumin (administration & dosage, immunology)
• Th2 Cells (immunology)
• Vaccines (administration & dosage, immunology)