Local Induction of a Specific Th1 Immune Response by Allergen Linked Immunostimulatory DNA in the Nasal Explants of Ragweed- Allergic Subjects

• Published in: Allergology International Vol. 58; no. 4; pp. 565 - 572
• Main Authors: Tulic, Meri K, Christodoulopoulos, Pota, Fiset, Pierre Olivier, Vaillancourt, Patrice, Lavigne, Francois, Marshall, Jason D, Van Nest, Gary, Eiden, Joseph J, Hamid, Qutayba
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 2009; JAPANESE SOCIETY OF ALLERGOLOGY; Elsevier
• Subjects: allergen; Allergens - genetics; Allergens - metabolism; allergic rhinitis; Ambrosia - immunology; Antigens, CD - metabolism; Antigens, Plant; Cells, Cultured; CpG motif; Cytokines - biosynthesis; Cytokines - genetics; Genetic Engineering; Humans; Immunization; Immunotherapy; Nasal Mucosa - immunology; Nasal Mucosa - metabolism; Nasal Mucosa - pathology; Oligodeoxyribonucleotides - genetics; Oligodeoxyribonucleotides - metabolism; Plant Proteins - genetics; Plant Proteins - metabolism; Pollen; Rhinitis, Allergic, Seasonal - immunology; Rhinitis, Allergic, Seasonal - therapy; Th1 Cells - immunology; Th2 Cells - immunology; vaccination; TT; allergen; Amb a 1; IL; RW; ICC; ISS; DNA; immunotherapy; APAAP; allergic rhinitis; AIC; CpG motif; vaccination; ISH
• ISSN: 1323-8930; 1440-1592
• DOI: 10.2332/allergolint.09-OA-0108

Allergen immunotherapy is effective in allergic individuals however efforts are being made to improve its safety, convenience, and efficacy. It has recently been demonstrated that allergen-linked immunostimulatory DNA (ISS) is effective in stimulating an allergen-specific Th1 response with decreased allergenicity. The objective of this study is to investigate whether ISS linked to purified ragweed allergen Amb-a-1 (AIC) can inhibit local allergen-specific Th2 and induce allergen-specific Th1 responses in explanted nasal mucosa of ragweed-sensitive subjects. In addition, we set out to determine whether AIC is more effective compared to stimulation with unlinked Amb a 1 and ISS.
Tissue from ragweed-sensitive patients (n=12) was cultured with whole ragweed allergen (RW), Amb-a-1, AIC, Amb-a-1 and ISS (unlinked), or tetanus toxoid (TT) for 24 hours. IL-4, −5, −13, TNF-α and IFN-γ mRNA-positive cells were visualized by in situ hybridization and T cells, B cells and neutrophils were enumerated using immunocytochemistry.
RW or Amb-a-1 increased the number of IL-4, IL-5, and IL-13 mRNA+cells in the tissue compared to medium alone. AIC had similar cytokine mRNA reactivity as control tissue. AIC and TT increased IFNγ-mRNA expression. Unlinked Amb-a-1 and ISS showed similar effects to AIC, however this response was weaker. The number of TNF mRNA+ cells, T cells, B cells and neutrophils remained unchanged.
AIC is effective in stimulating a local allergen-specific Th1- and abolishing Th2-cytokine mRNA reactivity in the nose and may be considered as a strong candidate for an improved approach to immunotherapy in ragweed-sensitive individuals.