La synapse immunologique : des modèles aux réalités

Abstract

Bien des années après avoir découvert que, à l’instar des neurones, les cellules du système immunitaire communiquent entre elles au niveau de jonctions spécialisées de type synapse, la fonction de ces structures est ainsi toujours discutée. La raison de ce questionnement persistant est sans doute à rechercher dans une surinterprétation de l’organisation moléculaire particulière que l’on observe dans des conditions expérimentales peu physiologiques à la jonction cellule T/cellule présentatrice d’antigène, et dans une généralisation abusive du modèle qui en a été tiré. L’ambition de cet article est donc de faire le point sur les limites d’une vision provisoirement dominante de la synapse immunologique, et de présenter un autre point de vue sur cette structure et son fonctionnement.

The notion of immunological synapse is generally associated to a concentric structure (a core of T cell receptors surrounded by a ring of adhesion molecules) often called “mature synapse”. This schematic view has been built on observations corresponding to peculiar experimental conditions: very high antigen concentration presented by surrogate APCs such as lipid bilayers or B lymphoma. These observations have been hastily constituted in a dogma that a “normal” synapse should look like this, should form only in the presence of antigen, and should trigger a “stop” signal that completely immobilizes the T cell. However, when analyzing the interaction between naive T cells and dendritic cells (DC), that are the only antigen-presenting cells able to activate naive T cells, a very different picture emerges. Firstly, T-DC synapses can form in the absence of antigen; therefore antigen recognition is not a prerequisite for synapse formation. Secondly, these antigen-independent synapses are likely to play several roles, including sensitization of T cells for later antigen detection, and delivery of survival signals. Thirdly, in vivo, naive T cells interacting with antigen-laden DC do not fully stop, but start to make transient contacts with DCs for a few minutes, before continuing their exploration. It is only after several hours of this process that T cells eventually immobilize. Fourthly, the structure of the T-DC synapse is clearly multifocal, the two cells interacting through several tens of tight appositions of a few tens of nm in diameter. These numerous tight appositions are reminiscent of the microclusters that have been recently described at the T-bilayer interface. Finally, synaptic signaling is not a transient initial event, but is sustained for hours. In particular, sustained activation of phosphatidylinositol 3-kinase allows the exclusion out of the nucleus of FoxO transcription factors, normally maintaining T cells in a quiescent state.