title: Monitoring the initiation and kinetics of human dendritic cell-induced polarization of autologous naive CD4+ T cells.
abstract: A crucial step in generating de novo immune responses is the polarization of naive cognate CD4+ T cells by pathogen-triggered dendritic cells (DC). In the human setting, standardized DC-dependent systems are lacking to study molecular events during the initiation of a naive CD4+ T cell response. We developed a TCR-restricted assay to compare different pathogen-triggered human DC for their capacities to instruct functional differentiation of autologous, naive CD4+ T cells. We demonstrated that this methodology can be applied to compare differently matured DC in terms of kinetics, direction, and magnitude of the naive CD4+ T cell response. Furthermore, we showed the applicability of this assay to study the T cell polarizing capacity of low-frequency blood-derived DC populations directly isolated ex vivo. This methodology for addressing APC-dependent instruction of naive CD4+ T cells in a human autologous setting will provide researchers with a valuable tool to gain more insight into molecular mechanisms occurring in the early phase of T cell polarization. In addition, it may also allow the study of pharmacological agents on DC-dependent T cell polarization in the human system.
authors.affiliation: Division of Hematology, Department of Internal Medicine, School of Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, the Netherlands.
authors.forename: Tammy
authors.initials: T
authors.lastname: Oth
authors.affiliation: Division of Hematology, Department of Internal Medicine, School of Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, the Netherlands.
authors.forename: Melanie C A
authors.initials: MC
authors.lastname: Schnijderberg
authors.affiliation: Division of Hematology, Department of Internal Medicine, School of Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, the Netherlands.
authors.forename: Birgit L M G
authors.initials: BL
authors.lastname: Senden-Gijsbers
authors.affiliation: Division of Hematology, Department of Internal Medicine, School of Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, the Netherlands.
authors.forename: Wilfred T V
authors.initials: WT
authors.lastname: Germeraad
authors.affiliation: Division of Hematology, Department of Internal Medicine, School of Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, the Netherlands.
authors.forename: Gerard M J
authors.initials: GM
authors.lastname: Bos
authors.affiliation: Tissue Typing Laboratory, Department of Transplantation Immunology, School of Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, the Netherlands.
authors.forename: Joris
authors.initials: J
authors.lastname: Vanderlocht
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D009000:Monocytes / Q000166:cytology; D016133:Polymerase Chain Reaction