title: How many dendritic cells are required to initiate a T-cell response?
abstract: T-cell activation in lymph nodes relies on encounters with antigen (Ag)-bearing dendritic cells (DCs) but the number of DCs required to initiate an immune response is unknown. Here we have used a combination of flow cytometry, 2-photon imaging, and computational modeling to quantify the probability of T cell-DC encounters. We calculated that the chance for a T cell residing 24 hours in a murine popliteal lymph nodes to interact with a DC was 8%, 58%, and 99% in the presence of 10, 100, and 1000 Ag-bearing DCs, respectively. Our results reveal the existence of a threshold in DC numbers below which T-cell responses fail to be elicited for probabilistic reasons. In mice and probably humans, we estimate that a minimum of 85 DCs are required to initiate a T-cell response when starting from precursor frequency of 10(-6). Our results have implications for the rational design of DC-based vaccines.
authors.affiliation: Institut Pasteur, Dynamics of Immune Responses Unit, Paris, France.
authors.forename: Susanna
authors.initials: S
authors.lastname: Celli
authors.forename: Mark
authors.initials: M
authors.lastname: Day
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Müller
authors.forename: Carmen
authors.initials: C
authors.lastname: Molina-Paris
authors.forename: Grant
authors.initials: G
authors.lastname: Lythe
authors.forename: Philippe
authors.initials: P
authors.lastname: Bousso
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D005802:Genes, MHC Class II / Q000276:immunology; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D013601:T-Lymphocytes / Q000276:immunology*