Amb a 1-immunostimulatory oligodeoxynucleotide conjugate immunotherapy increases CD4+CD25+ T cells in the nasal mucosa of subjects with allergic rhinitis.
BACKGROUND
We have previously shown that short-course treatment with Amb a 1-immunostimulatory phosphorothioate oligonucleotide conjugate (AIC) before the ragweed season modifies the response of the nasal mucosa to allergen challenge in ragweed-sensitive patients by increasing Th1 cytokines and decreasing both Th2 cytokines and eosinophilia after the ragweed season. The effect of AIC immunotherapy on CD4+CD25+ T cell expression in the nasal mucosa is unknown.


OBJECTIVE
To determine the in vivo effect of short-course AIC immunotherapy on CD4+CD25+ regulatory T cells in the nasal mucosa of ragweed-sensitive subjects.


METHODS
19 ragweed-sensitive patients with allergic rhinitis were randomly assigned to receive either 6 escalating doses of AIC (0.06-12microg; n = 12) or placebo (n = 7) at weekly intervals immediately before the 2001 ragweed season. Nasal biopsies were taken at baseline prior to immunization and again post immunization 24 hours after ragweed allergen challenge at the start and end of the ragweed season. The expression of T regulatory cells, IL-10 and TGF-beta was assessed at each time point by immunohistochemistry.


RESULTS
The numbers of allergen-induced CD4+-, CD4+CD25+-, IL-10- and TGF-beta-positive cells in the nasal mucosa after AIC immunization before the ragweed season did not differ between the two groups. Repeat challenge after the ragweed season led to a significant increase in CD4+CD25+ cells in AIC-compared with placebo-treated subjects. A trend toward an increase in IL-10-positive cells in the AIC-treated group did not reach statistical significance.


CONCLUSIONS
Short-course AIC immunotherapy increases CD4+CD25+ regulatory T cell infiltration in the nasal mucosa following allergen challenge after seasonal ragweed-pollen exposure.
Asai
Kazuhisa
K
Meakins-Christie Laboratories, McGill University, Quebec, Canada.
Foley
Susan C
SC
Sumi
Yuki
Y
Yamauchi
Yasuhiro
Y
Takeda
Naoya
N
Desrosiers
Martin
M
Lavigne
François
F
Hamid
Qutayba
Q
D000485:Allergens / Q000276:immunology / Q000627:therapeutic use*; D031164:Ambrosia / Q000276:immunology; D052179:Antigens, Plant; D001706:Biopsy; D015704:CD4 Antigens; D002452:Cell Count; D003888:Desensitization, Immunologic; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit; D008213:Lymphocyte Activation / Q000276:immunology; D009297:Nasal Mucosa / Q000276:immunology / Q000473:pathology; D054735:Phosphorothioate Oligonucleotides / Q000276:immunology / Q000627:therapeutic use*; D010940:Plant Proteins / Q000276:immunology / Q000627:therapeutic use*; D011058:Pollen / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology* / Q000517:prevention & control; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000485:Allergens; C026967:Amb a I protein, Ambrosia artemisiifolia; D052179:Antigens, Plant; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D054735:Phosphorothioate Oligonucleotides; D010940:Plant Proteins; D016212:Transforming Growth Factor beta; D016753:Interleukin-10