Dendritic cell activation of CD8+ T cells at the immunological synapse is critical for immunity, but the structural organization of the dendritic cell side and its impact on T cell fate remain poorly defined. Using bone marrow-derived dendritic cells (BMDCs) as a model, we describe two stable subpopulations distinguished by their capacity to form morphologically distinct synapses.
We demonstrate that this architectural divergence is governed by the differential expression of the co-stimulatory molecule CD70: CD70high BMDCs form spiky “firework” synapses driven by a filopodia-based cytoskeletal program, while CD70low BMDCs form smooth “pancake” synapses. This structural dichotomy functionally dictates T cell programming.
CD70high dendritic cells prime potent, terminally differentiated Tc1 effector cells. In contrast, IL-6-secreting CD70low dendritic cells generate memory T cells with a Tc17-like functional profile and robust recall capacity.
Our work reveals that DC synapse architecture is a key determinant of T cell fate, linking the physical organization of the cell to distinct immunological outcomes.
Frontiers in Immunology published a clinical update in Infectious Disease on 01 Apr 2026.
The item focuses on Distinct dendritic cell cytoskeletal programs dictate synapse architecture and CD8+ T cell fate.
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