Differential activation of dendritic cells by toll‐like receptors causes diverse differentiation of naïve CD4+ T cells from allergic patients. Issue 12 (3rd October 2014)

• Record Type: Journal Article
• Authors: Deifl, S.; Kitzmüller, C.; Steinberger, P.; Himly, M.; Jahn‐Schmid, B.; Fischer, G. F.; Zlabinger, G. J.; Bohle, B.
• Is Part Of: Allergy. Volume 69:Issue 12(2014:Dec.)
• Page Start: 1602
• Page End: 1609
• Publication Date: 2014-10-03
• Subjects: Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.12501
• Languages: English
• ISSNs: 0105-4538

Abstract

<abstract abstract-type="main" id="all12501-abs-0001"> <title>Abstract</title> <sec id="all12501-sec-0001" sec-type="section"> <title>Background</title> <p>To avert the differentiation of allergen‐specific Th2 cells in atopic individuals is a major goal in the prevention and therapy of IgE‐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.</p> </sec> <sec id="all12501-sec-0002" sec-type="section"> <title>Methods</title> <p>Monocytes and monocyte‐derived dendritic cells (mdDC) from allergic patients were stimulated with Pam3CSK4 (TLR1/2 ligand), FSL‐1 (TLR2/6 ligand), monophosphoryl lipid (MPL)‐A, lipopolysaccharide (LPS, both TLR4 ligands), and flagellin (TLR5 ligand). Allergen uptake and upregulation of CD40, CD80, CD83, CD86, CD58, CCR7 and PD‐L1 were analyzed by flow cytometry. Functional maturation of mdDC 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 mdDC were used to stimulate naïve CD4<sup>+</sup> T cells, and cytokine responses were assessed in supernatants and intracellularly.</p> </sec> <sec id="all12501-sec-0003" sec-type="section"> <title>Results</title> <p>All TLR ligands except flagellin enhanced allergen uptake. All TLR ligands induced functional maturation of mdDC with differential expression of surface molecules and cytokines and promoted the differentiation of IFN‐γ‐producing T cells. LPS‐matured mdDC exclusively induced Th1‐like responses, whereas mdDC stimulated with the other TLR ligands induced both Th1‐ and Th0‐like cells. Pam3CSK4 and flagellin additionally induced Th2‐like cells. Th1‐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 mdDC induced IL‐10‐ or IL‐17‐producing T cells.</p> </sec> <sec id="all12501-sec-0004" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> </abstract>