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Review
. 2016 Mar 7:7:70.
doi: 10.3389/fimmu.2016.00070. eCollection 2016.

The Dendritic Cell Synapse: A Life Dedicated to T Cell Activation

Federica Benvenuti  1
Affiliations
Review

The Dendritic Cell Synapse: A Life Dedicated to T Cell Activation

Federica Benvenuti. Front Immunol. .

Abstract

T-cell activation within immunological synapses is a complex process whereby different types of signals are transmitted from antigen-presenting cells to T cells. The molecular strategies developed by T cells to interpret and integrate these signals have been systematically dissected in recent years and are now in large part understood. On the other side of the immune synapse, dendritic cells (DCs) participate actively in synapse formation and maintenance by remodeling of membrane receptors and intracellular content. However, the details of such changes have been only partially characterized. The DCs actin cytoskeleton has been one of the first systems to be identified as playing an important role in T-cell priming and some of the underlying mechanisms have been elucidated. Similarly, the DCs microtubule cytoskeleton undergoes major spatial changes during synapse formation that favor polarization of the DCs subcellular space toward the interacting T cell. Recently, we have begun to investigate the trafficking machinery that controls polarized delivery of endosomal vesicles at the DC-T immune synapse with the aim of understanding the functional relevance of polarized secretion of soluble factors during T-cell priming. Here, we will review the current knowledge of events occurring in DCs during synapse formation and discuss the open questions that still remain unanswered.

Keywords: actin cytoskeleton; antigen presentation; dendritic cells; immune synapse; polarized secretion.

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Figures

Figure 1
Figure 1
Actin remodeling at the DC-IS. F-actin filaments become polarized and cluster enriched at the junction with an antigen-specific T cells. Fascin, an actin-bundling protein implicated in extension of membrane protrusion and development of dendrites is enriched in this area and controls the capacity of DCs to activate T cells. The Rho GTPase Rac is required for synapse formation and T-cell activation, likely via WAVE-mediated actin remodeling. WASp is a further activator of the Arp2/3 complex that is essential to support the antigen-presenting activities of DCs by promoting actin branching, thereby stabilizing the synaptic structure. WASp activation is mediated by cdc42 that is also found enriched at the DC-IS. The formin family mDia, involved in elongation of long actin filaments is important to establish and stabilize DC–T contacts and to support T-cell activation.
Figure 2
Figure 2
Polarized delivery of cytokine at the DC-IS. Upon contact with antigen-specific T cells DCs reorient the centrosome toward the interacting T cell. Polarization depends on the Rho GTPase cdc42. Newly synthesized IL-12 is contained in intracellular vesicles that cluster in the Golgi area and are readily redistribute at the IS upon antigen-specific contact formation. Release of IL-12 in the synaptic cleft induces activation of STAT4 and triggering of IFN-γ in the interacting T cell.
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