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* Centre d’Immunologie Institut National de la Santé et de la Recherche Médicale-Centre National de la Recherche Scientifique-Université de la Méditerranée de Marseille-Luminy, Marseille, France;
Institut National de la Santé et de la Recherche Médicale Unité 396, Immunogénétique Humaine, Centre de Recherches Biomédicales des Cordeliers, Paris, France; and
Centre National de la Recherche Scientifique Groupement de Recherche 2352, Marseille, France
We investigated differentiation of CD4 T cells responding to Ag presented by bone marrow-derived dendritic cells (DC) in association with MHC class II (MHC II) molecules. Peptides encapsulated in liposomes opsonized by IgG were taken up by endocytosis. MHC II-peptide-specific T cells responding to this Ag were polarized to a Th1 cytokine profile in a CD40-, CD28-, MyD88-, and IL-12-dependent manner. Th2 responses were obtained from the same transgenic T cell population exposed to the same DC on which MHC-peptide complexes had dispersed for 48 h following uptake of FcR-targeted liposomes. DC that took up the same FcR-targeted liposomes and then were exposed to methyl-
-cyclodextrin, which chelates cholesterol and dissociates lipid microdomains, also stimulated Th2 differentiation. Incubation of T cells with DC incubated with peptides directly binding to MHC II resulted in Th2 responses, whether or not the DC were coincubated with opsonized liposomes as a maturation stimulus. CD4 Th1 polarization thus appears to depend on MHC II-peptide complex clustering in DC lipid microdomains and the time between peptide loading and T cell encounter.
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