title: Prolonged costimulation is required for naive T cell activation.
abstract: Costimulation by members of the B7 family of molecules is critical for the activation of naive CD4+ T cells. While prolonged TCR signaling is necessary for T cell activation, the duration of costimulatory signals required has not been established. In this study, murine bone marrow-derived dendritic cells (DC) and naïve CD4+ T cells were used to determine the temporal costimulatory requirements for naive T cell activation. By blocking CD80/CD86 costimulation at various time points during DC-T cell interaction and using the CFSE technique to assess the dynamics of T cell proliferation, we found that prolonged costimulation was required for naive T cells to enter and progress through the cell cycle over a wide range of peptide concentrations. Prolonged costimulation was also important for IL-2 production and CD25/CD69 expression by naive T cells. Video microscopy demonstrated that DC and naive T cells formed stable conjugates that persisted for more than 6 h. Thus, persistent CD80/CD86 signaling during prolonged interactions with DC allows naive T cells to enter the cell cycle and programs the daughter cells to undergo subsequent divisions.
authors.affiliation: Department of Pathology, Dalhousie University, Halifax, NS, Canada.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Liwski
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Chase
authors.forename: William H
authors.initials: WH
authors.lastname: Baldridge
authors.forename: Irene
authors.initials: I
authors.lastname: Sadek
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Rowden
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: West
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002453:Cell Cycle / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018715:Microscopy, Video; D015398:Signal Transduction / Q000276:immunology*; D013997:Time Factors
chemical_list: D015703:Antigens, CD