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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Tulic
Meri K
MK
School of Pediatrics & Child Health, University of Western Australia, Australia. merit@ichr.uwa.edu.au
Christodoulopoulos
Pota
P
Fiset
Pierre Olivier
PO
Vaillancourt
Patrice
P
Lavigne
Francois
F
Marshall
Jason D
JD
Van Nest
Gary
G
Eiden
Joseph J
JJ
Hamid
Qutayba
Q
D000485:Allergens / Q000235:genetics / Q000378:metabolism*; D031164:Ambrosia / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D052179:Antigens, Plant; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005818:Genetic Engineering; D006801:Humans; D007114:Immunization; D007167:Immunotherapy; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000378:metabolism*; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism*; D011058:Pollen; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology* / Q000628:therapy; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D000485:Allergens; C026967:Amb a I protein, Ambrosia artemisiifolia; D015703:Antigens, CD; D052179:Antigens, Plant; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D010940:Plant Proteins