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Summary  A strategy to improve allergen‐specific immunotherapy is to employ new adjuvants stably linked to allergens. The study is addressed to evaluate the  in vivo  and  in vitro  effects of allergens [natural  Dermatophagoides pteronyssinus  2 (  nD er p  2) and ovalbumin ( OVA )] chemically bound to an 8‐ OH ‐modified adenine. Humoral and cellular responses were analysed in allergen‐sensitized and challenged mice by using conjugates (Conj) in a therapeutic setting. The  in vitro  activity of the conjugates on cytokine production induced by bone marrow dendritic cells and the co‐culture system was also investigated. The   nD er p  2‐Conj treatment in   nD er p  2‐primed and challenged  BALB /c mice reduced the numbers of eosinophils in bronchoalveolar lavage fluid and lung, airway allergen‐driven interleukin‐13 ( IL ‐13) production in lung mononuclear cells and IgE, in comparison with   nD er p  2‐treated mice. The increase of IgG2a paralleled that of interferon‐ γ  ( IFN ‐ γ ) and  IL ‐10 in allergen‐stimulated spleen cells. Similar effects were elicited by treatment with  OVA ‐Conj in an  OVA ‐driven  BALB /c model. The   nD er p  2‐Conj or  OVA ‐Conj redirected memory  T  helper type 2 cells towards the production of  IL ‐10 and  IFN ‐ γ  also in C57BL/6 mice and when subcutaneously administered. Interleukin‐10,  IL ‐12 and  IL ‐27 were produced  in vitro  by Conj‐stimulated bone marrow dendritic cells, whereas  IL ‐10 and  IFN ‐ γ  were up‐regulated in co‐cultures of  CD 11c +  and  CD 4 +  T cells from Conj‐treated mice stimulated with allergen. Cytofluorometric analysis indicated that the Conj expanded  IFN ‐ γ ‐ and  IL ‐10‐ producing memory T cells. The Conj effects on  IL ‐10 −/−  and  IL ‐12 −/−  mice confirmed the role of  IL ‐10 and  IFN ‐ γ  in inducing a protective and balanced redirection the  T  helper type 2‐mediated airway inflammation.

Treatment with 8‐ OH ‐modified adenine ( TLR 7 ligand)‐allergen conjugates decreases T helper type 2‐oriented murine airway inflammation