The Toll-Like Receptor-2/6 Agonist Macrophage-Activating Lipopeptide-2 Cooperates with IFN-γ to Reverse the Th2 Skew in an In Vitro Allergy Model
| Autor: | Armin Braun, Henning Weigt, Peter F. Mühlradt, Norbert Krug, M. Larbig |
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| Rok vydání: | 2004 |
| Předmět: |
Hypersensitivity
Immediate Agonist Allergy medicine.drug_class Immunology Receptors Cell Surface Biology Arthropod Proteins Interferon-gamma Lipopeptides chemistry.chemical_compound Th2 Cells Immune system Bacterial Proteins medicine Humans Immunology and Allergy Macrophage Antigens Dermatophagoides Receptor Cells Cultured Toll-like receptor Membrane Glycoproteins Toll-Like Receptors Lipopeptide Drug Synergism Dendritic Cells Macrophage Activation Th1 Cells medicine.disease Interleukin-12 Coculture Techniques Lymphocyte Subsets Toll-Like Receptor 2 In vitro Cysteine Endopeptidases Drug Combinations Protein Subunits Toll-Like Receptor 6 chemistry Interleukin-4 Oligopeptides Cell Division |
| Zdroj: | The Journal of Immunology. 172:6080-6086 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Dendritic cells (DC) are the most potent APCs with the capacity to induce, modulate, or shut down immune function. These features make them potentially useful for treating diseases associated with misled immunologic responses. Therefore, it was the aim of this study to reverse the allergen-dependent Th2 reaction responsible for allergic symptoms by modulating DC function. This issue was addressed in an in vitro test system consisting of human monocyte-derived allergen-pulsed DC from allergics cocultured with autologous lymphocytes. A Th2 reaction judged by the amplification of IL-4 and the down-regulation of IFN-γ was induced by pulsing DC with the relevant allergen. To modulate this reaction, the Toll-like receptor 2/6 engaging mycoplasmal lipopetide macrophage-activating lipopeptide 2 kDa was combined with IFN-γ to stimulate allergen-pulsed DC. Such treatment resulted in a 500-fold increase in IFN-γ production in the supernatant of cocultured autologous lymphocytes, while the Th2 marker IL-4 was not affected. This phenomenon was associated with an increase in proliferation and the number of IFN-γ-producing lymphocytes. Phenotype and function of thus treated DC remained stable. These data indicate that a former allergen-dependent Th2 reaction can be reversed toward a Th1-type response by an appropriate treatment of DC. |
| Databáze: | OpenAIRE |
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