Abstract

In cells of the immune system, the secretion of extracellular vesicles is modulated through cellular activation. In particular, T cell activation is achieved through cell–cell contacts with antigen presenting cells and the consequent formation of a specialized signaling junction called the immunological synapse. Recent works on CD4 T cells have elucidated that cognate antigen recognition by the T cell receptor (TCR) engages two distinct exocytic events. The first involves the exocytic targeting of signaling molecules at the synaptic membrane and drives the functional architecture of the immunological synapse. The second enlists the extracellular secretion of the TCR itself, once the functional architecture of the immunological synapse is accomplished. HIV-1, a human lymphotropic virus, has evolved sophisticated mechanisms to co-opt CD4 T cell physiology. Notably, it has become apparent that HIV-1 intersects the regulated secretory system of CD4 T cells in order to bud from the plasma membrane of the infected cell and to promote bystander cell death. Here, I review the relevance of CD4 vesicle exocytosis to immune regulation and to HIV-1 pathogenesis and discuss their potential therapeutic applications.

Highlights

  • The mounting of an immune response relies on the efficiency of intercellular communication

  • The immunological synapse consists of a tightly structured signaling platform induced upon T cell receptor (TCR) recognition of the cognate antigen–MHC complexes presented on the surface of the antigen-presenting cells (APCs)

  • The immunological synapse is emerging as a hotspot for vesicle-mediated processes, encompassing exocytic targeting of vesicles containing signaling molecules [1, 2], the polarized secretion of cytokines [3], the release of extracellular vesicles carrying membrane-associated molecules [TCR [4, 5], Fas ligand (FasL) [8], and cytotoxic T lymphocyte antigen-4 (CTLA-4) [9]], and the release of extracellular vesicles containing genetical material in the form of microRNA [6, 7]

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Summary

Introduction

The mounting of an immune response relies on the efficiency of intercellular communication. Recent works have elucidated that the specificity of T cell–APC communication is achieved through the compounded action of the exocytic targeting of signaling molecules and cytokines and through the extracellular vesicle exchange at the immunological synapse. There is increasing evidence that HIV-1 coopts CD4 T cells-regulated secretion of extracellular vesicles in order to modulate the host immune response and to increase its propagation.

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