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CD4 T cells integrate signals delivered during successive DC encounters in vivo
Susanna Celli1, Zacarias Garcia, Philippe Bousso
1G5 Dynamiques des Réponses Immunes, INSERM 668, Département d'Immunologie, Institut Pasteur, Paris, France.
Insights
Activated T cells re-encounter antigen-presenting dendritic cells (DCs) multiple times in lymph nodes. These repeated interactions are crucial for sustained T cell activation, IL-2Ralpha expression, and IFN-gamma production, influencing T cell differentiation.
Area of Science:
- Immunology
- Cell Biology
- T cell activation
Background:
- The precise cellular mechanisms governing T cell priming in vivo are not fully understood.
- T cell-dendritic cell (DC) interactions are central to initiating adaptive immune responses.
- The dynamics of T cell-DC interactions during the later stages of T cell activation require further elucidation.
Purpose of the Study:
- To investigate the fate and function of T cell-DC interactions during the late phase of T cell activation in lymph nodes.
- To characterize the re-engagement patterns of activated T cells with DCs.
- To determine the impact of subsequent DC contacts on T cell signaling and differentiation.
Main Methods:
- Utilized a novel approach to track antigen (Ag)-recognition events in T cells.
- Employed two-photon imaging to visualize T cell-DC interactions within intact lymph nodes.
- Monitored T cell responses including IL-2Ralpha expression and IFN-gamma production.
Main Results:
- Activated CD4 T cells detach from initial DCs before division but subsequently re-engage different DCs in an antigen-specific manner.
- Prolonged T cell-DC interactions occur at multiple stages of the activation process.
- Subsequent DC contacts integrate signals, sustaining IL-2Ralpha expression and promoting IFN-gamma production.
Conclusions:
- Repeated encounters between T cells and antigen-bearing DCs occur in vivo.
- These subsequent interactions are critical for modulating CD4 T cell differentiation programs.
- The findings reveal a dynamic model of T cell priming involving iterative DC engagement.
Abstract:
The cellular mode of T cell priming in vivo remains to be characterized fully. We investigated the fate of T cell-dendritic cell (DC) interactions in the late phase of T cell activation in the lymph node. In general, CD4 T cells detach from DCs before undergoing cell division. Using a new approach to track the history of antigen (Ag)-recognition events, we demonstrated that activated/divided T cells reengage different DCs in an Ag-specific manner. Two-photon imaging of intact lymph nodes suggested that T cells could establish prolonged interactions with DCs at multiple stages during the activation process. Importantly, signals that are delivered during subsequent DC contacts are integrated by the T cell and promote sustained IL-2Ralpha expression and IFN-gamma production. Thus, repeated encounters with Ag-bearing DCs can occur in vivo and modulate CD4 T cell differentiation programs.
