Prolonged costimulation is required for naive T cell activation.
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.
Liwski
Robert S
RS
Department of Pathology, Dalhousie University, Halifax, NS, Canada.
Chase
Jennifer C
JC
Baldridge
William H
WH
Sadek
Irene
I
Rowden
Geoffrey
G
West
Kenneth A
KA
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
D015703:Antigens, CD