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Updated: Aug 7, 2026
Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist
Published on: April 25, 2018
Prolonged costimulation is required for naive T cell activation
Robert S Liwski1, Jennifer C Chase, William H Baldridge
1Department of Pathology, Dalhousie University, Halifax, NS, Canada.
Insights
Prolonged costimulation via CD80/CD86 is essential for naive CD4+ T cell activation, IL-2 production, and cell cycle progression. Persistent signaling during dendritic cell interactions programs T cells for sustained division.
Area of Science:
- Immunology
- Cellular Biology
Background:
- Naive CD4+ T cell activation requires T cell receptor (TCR) signaling and costimulation from B7 family molecules.
- The precise duration of costimulatory signals needed for T cell activation remains unclear.
Purpose of the Study:
- To investigate the temporal requirements of CD80/CD86 costimulation for naive T cell activation.
- To understand the role of signal duration in T cell proliferation, cytokine production, and surface marker expression.
Main Methods:
- Utilized murine bone marrow-derived dendritic cells (DCs) and naive CD4+ T cells.
- Employed CD80/CD86 costimulation blockade at different time points during DC-T cell interactions.
- Assessed T cell proliferation dynamics using the CFSE technique and observed cell-cell interactions via video microscopy.
Main Results:
- Prolonged CD80/CD86 costimulation is necessary for naive T cells to initiate and advance through the cell cycle across various peptide concentrations.
- Sustained costimulation significantly impacts interleukin-2 (IL-2) production and the expression of CD25 and CD69 on naive T cells.
- Video microscopy revealed stable DC-T cell conjugates persisting for over 6 hours, indicating prolonged interaction.
Conclusions:
- Persistent CD80/CD86 signaling during extended DC-T cell interactions is crucial for naive T cell entry into the cell cycle.
- This sustained signaling also programs subsequent cell divisions and immune responses.
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.
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