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Differential activation of dendritic cells by toll‐like receptors causes diverse differentiation of naïve CD 4 + T cells from allergic patients
Author(s) -
Deifl S.,
Kitzmüller C.,
Steinberger P.,
Himly M.,
JahnSchmid B.,
Fischer G. F.,
Zlabinger G. J.,
Bohle B.
Publication year - 2014
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12501
Subject(s) - receptor , toll , immunology , microbiology and biotechnology , chemistry , biology , biochemistry
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.