Imaging regulatory T cell dynamics and CTLA4-mediated suppression of T cell priming

Foxp3 + regulatory T cells (Tregs) maintain immune homoeostasis through mechanisms that remain incompletely defined. Here by two-photon (2P) imaging, we examine the cellular dynamics of endogenous Tregs. Tregs are identified as two non-overlapping populations in the T-zone and follicular regions of the lymph node (LN). In the T-zone, Tregs migrate more rapidly than conventional T cells (Tconv), extend longer processes and interact with resident dendritic cells (DC) and Tconv. Tregs intercept immigrant DCs and interact with antigen-induced DC:Tconv clusters, while continuing to form contacts with activated Tconv. During antigen-specific responses, blocking CTLA4-B7 interactions reduces Treg–Tconv interaction times, increases the volume of DC:Tconv clusters and enhances subsequent Tconv proliferation in vivo . Our results demonstrate a role for altered cellular choreography of Tregs through CTLA4-based interactions to limit T-cell priming. T regulatory cells (Tregs) prevent immunopathology by inhibiting excessive T-cell activation. Here the authors show interactions between dendritic cells, Tregs and antigen-specific T cells in the lymph node during initiation of the immune response in real time by two-photon microscopy.