Structure and duration of contact between dendritic cells and T cells are controlled by T cell activation state

Abstract The adaptive immune response is initiated when naive T cells interact with dendritic cells (DC). However, the physicodynamics as well as the molecules that constitute the contact plane (immunological synapse) between DC and T cells are not well understood. We show here that for the formation of stable conjugates, T cells need to be preactivated by DC in a CD80/86‐ and antigen dose‐dependent manner. When activated, T cells induce cytoskeletal reorganization within DC via CD40‐CD40L signaling. Polarization of the actin and fascin cytoskeleton in DC is associated with sustained DC‐T cell contacts, strong T cell proliferation and a Th1 response. Organized contact planes with clearly separated patches containing TCR or CD11a are also formed. Thus, DC‐T cell interactions take place in a sequential, interdependent fashion: first, DC “license” naive T cells to engage DC in an antigen dose‐ and CD80/86‐dependent fashion. Then, these preactivated T cells induce cytoskeletal reorientation in DC, resulting in sustained DC‐T cell contacts and subsequent T cell activation. These results demonstrate that T cells control the mode of interaction based on information gathered from DC.