Local induction of a specific Th1 immune response by allergen linked immunostimulatory DNA in the nasal explants of ragweed-allergic subjects.

Meri K Tulic, Pota Christodoulopoulos, Pierre Olivier Fiset, Patrice Vaillancourt, Francois Lavigne, Jason D Marshall, Gary Van Nest, Joseph J Eiden, Qutayba Hamid

School of Pediatrics & Child Health, University of Western Australia, Australia. merit@ichr.uwa.edu.au

Allergology international : official journal of the Japanese Society of Allergology 2009 Dec

filter terms:

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-alpha and IFN-gamma 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 IFNgamma-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.

Citation

Meri K Tulic, Pota Christodoulopoulos, Pierre Olivier Fiset, Patrice Vaillancourt, Francois Lavigne, Jason D Marshall, Gary Van Nest, Joseph J Eiden, Qutayba Hamid. Local induction of a specific Th1 immune response by allergen linked immunostimulatory DNA in the nasal explants of ragweed-allergic subjects. Allergology international : official journal of the Japanese Society of Allergology. 2009 Dec;58(4):565-72