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The Toll-Like Receptor-2/6 Agonist Macrophage-Activating Lipopeptide-2 Cooperates with IFN- to Reverse the Th2 Skew in an In Vitro Allergy Model¹

Henning Weigt^2,*, Peter F. Muhlradt, Michael Larbig^*, Norbert Krug^* and Armin Braun^*

^* Fraunhofer Institute of Toxicology and Experimental Medicine, Department of Immunology, Allergology, and Clinical Inhalation, Hannover, Germany; and Wound Healing Research Group, Gruenderzentrum, Braunschweig, Germany

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- 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- to stimulate allergen-pulsed DC. Such treatment resulted in a 500-fold increase in IFN- 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--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.

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