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Published on: July 9, 2008
Imaging the single cell dynamics of CD4+ T cell activation by dendritic cells in lymph nodes
Mark J Miller1, Olga Safrina, Ian Parker
1Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA.
Insights
Naive CD4+ T cells interact with dendritic cells (DCs) in lymph nodes through short, serial contacts. This dynamic process, observed in vivo, suggests T cell activation occurs via multiple antigen recognition events.
Area of Science:
- Immunology
- Cell Biology
- In vivo imaging
Background:
- Adaptive immune responses initiate in lymphoid organs via dendritic cell (DC) and T cell interactions.
- Limited understanding exists regarding the in vivo single-cell dynamics of T cell-DC interactions.
Purpose of the Study:
- To visualize and characterize the real-time, in vivo behavior of naive CD4+ T cells and DCs within lymph nodes during an immune response.
Main Methods:
- Utilized two-photon microscopy to image naive CD4+ T cells and in vivo-labeled DCs in lymph nodes.
- Analyzed T cell motility patterns and contact durations with DCs.
Main Results:
- T cells exhibited short-lived contacts (avg. 11-12 min) with DCs, primarily on dendrites, within the first 2 hours post-entry.
- T cell motility changes facilitated serial engagement with multiple DCs.
- Observed distinct behavioral stages: short contacts, clusters, swarms, and autonomous migration with cell division.
Conclusions:
- The immunological synapse in vivo is dynamic, with stable synapses forming only at specific antigen presentation stages.
- Serial interactions suggest T cell activation relies on multiple antigen recognition events.
Abstract:
The adaptive immune response is initiated in secondary lymphoid organs by contact between antigen-bearing dendritic cells (DCs) and antigen-specific CD4+ T cells. However, there is scant information regarding the single cell dynamics of this process in vivo. Using two-photon microscopy, we imaged the real-time behavior of naive CD4+ T cells and in vivo-labeled DCs in lymph nodes during a robust T cell response. In the first 2 h after entry into lymph nodes, T cells made short-lived contacts with antigen-bearing DCs, each contact lasting an average of 11-12 min and occurring mainly on dendrites. Altered patterns of T cell motility during this early stage of antigen recognition promoted serial engagement with several adjacent DCs. Subsequently, T cell behavior progressed through additional distinct stages, including long-lived clusters, dynamic swarms, and finally autonomous migration punctuated by cell division. These observations suggest that the immunological synapse in native tissues is remarkably fluid, and that stable synapses form only at specific stages of antigen presentation to T cells. Furthermore, the serial nature of these interactions implies that T cells activate by way of multiple antigen recognition events.

