Imaging the Single Cell Dynamics of CD4+ T Cell Activation by Dendritic Cells in Lymph Nodes

TLDR

The adaptive immune response begins in secondary lymphoid organs when antigen‑bearing dendritic cells contact antigen‑specific CD4⁺ T cells, yet the single‑cell dynamics of this interaction in vivo remain poorly understood. The study aimed to visualize the real‑time behavior of naive CD4⁺ T cells and dendritic cells in lymph nodes during a robust T cell response using two‑photon microscopy. Two‑photon microscopy was employed to image naive CD4⁺ T cells and in vivo‑labeled dendritic cells in lymph nodes during a robust T cell response. Within the first two hours after lymph node entry, T cells formed short‑lived contacts (11–12 min) mainly on dendrites, then altered motility promoted serial engagement with adjacent DCs; later stages included long‑lived clusters, dynamic swarms, and autonomous migration with division, indicating a fluid immunological synapse that forms only at specific stages and that T cells activate through 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.