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Background  To avert the differentiation of allergen‐specific  T h2 cells in atopic individuals is a major goal in the prevention and therapy of  I g E ‐mediated allergy. We aimed to compare different toll‐like receptor ( TLR ) agonists regarding their effects on antigen‐presenting cells and the differentiation of naïve  T  cells from allergic patients.    Methods  Monocytes and monocyte‐derived dendritic cells (md DC ) from allergic patients were stimulated with  P am3 CSK 4 ( TLR 1/2 ligand),  FSL ‐1 ( TLR 2/6 ligand), monophosphoryl lipid ( MPL )‐ A , lipopolysaccharide ( LPS , both  TLR 4 ligands), and flagellin ( TLR 5 ligand). Allergen uptake and upregulation of  CD 40,  CD 80,  CD 83,  CD 86,  CD 58,  CCR 7 and  PD ‐ L 1 were analyzed by flow cytometry. Functional maturation of md DC  was tested in mixed leukocyte reactions, and the synthesis of proinflammatory cytokines,  IL ‐10 and members of the  IL ‐12 family was assessed.  TLR ‐ligand‐activated md DC  were used to stimulate naïve  CD 4 +   T  cells, and cytokine responses were assessed in supernatants and intracellularly.    Results  All  TLR  ligands except flagellin enhanced allergen uptake. All  TLR  ligands induced functional maturation of md DC  with differential expression of surface molecules and cytokines and promoted the differentiation of  IFN ‐γ‐producing  T  cells.  LPS ‐matured md DC  exclusively induced  T h1‐like responses, whereas md DC  stimulated with the other  TLR  ligands induced both  T h1‐ and  T h0‐like cells.  P am3 CSK 4 and flagellin additionally induced  T h2‐like cells.  T h1‐like responses were associated with higher expression levels of co‐stimulatory molecules,  PD ‐L1,  IL ‐6,  TNF ‐α, and  IL ‐12p70. None of the  TLR ‐ligand‐stimulated md DC  induced  IL ‐10‐ or  IL ‐17‐producing  T  cells.    Conclusion  Different  TLR  ligands differently influence  T ‐cell responses due to varying activation of the three signals relevant for  T ‐cell activation, that is, antigen presentation, co‐stimulation and cytokine milieu.

Differential activation of dendritic cells by toll‐like receptors causes diverse differentiation of naïve CD 4 + T cells from allergic patients