Abstract
Exosomes are extracellular vesicles (EV) of endosomal origin (multivesicular bodies, MVB) constitutively released by many different eukaryotic cells by fusion of MVB to the plasma membrane. However, inducible exosome secretion controlled by cell surface receptors is restricted to very few cell types and a limited number of cell surface receptors. Among these, exosome secretion is induced in T lymphocytes and B lymphocytes when stimulated at the immune synapse (IS) via T-cell receptors (TCR) and B-cell receptors (BCR), respectively. IS formation by T and B lymphocytes constitutes a crucial event involved in antigen-specific, cellular, and humoral immune responses. Upon IS formation by T and B lymphocytes with antigen-presenting cells (APC), the convergence of MVB towards the microtubule organization center (MTOC), and MTOC polarization to the IS, are involved in polarized exosome secretion at the synaptic cleft. This specialized mechanism provides the immune system with a finely-tuned strategy to increase the specificity and efficiency of crucial secretory effector functions of B and T lymphocytes. As inducible exosome secretion by antigen-receptors is a critical and unique feature of the immune system this review considers the study of the traffic events leading to polarized exosome secretion at the IS and some of their biological consequences.
Highlights
A Brief History of ExosomesExosomes are small membrane vesicles (50–150 nm) secreted by a multitude of cell types as a consequence of the fusion of multivesicular bodies (MVB) with the plasma membrane [1,2]
The fact that peptide-MHC-II complexes (pMHC-II) on exosomes secreted from activated B lymphocytes efficiently stimulate primed antigen-specific T lymphocytes (Th) lymphocytes suggests a positive role of B-lymphocyte derived exosomes in the maintenance of an ongoing immune response [16]
During the last 15 years, exosomes have been studied as new biological entities involved in intercellular communication during a multitude of physiological and pathological processes, in particular in the context of the immune system
Summary
Exosomes are small membrane vesicles (50–150 nm) secreted by a multitude of cell types as a consequence of the fusion of multivesicular bodies (MVB) with the plasma membrane [1,2]. UScinticoen t[h1e1n]., an (ibiemnmxephp2iRlaSuibf0oomuviNo1prnsni9ttmiocAahcto,eortnunF)im,totmn[ihi1gnwnRode3ouacNnhit]rlrosh.,eieccAmceAahoth1nhfapvna)inaeeecoenanglartxtddneyhnipn2ndemol6gtobwrf0aiscermeca0ieeroxrsdlceaoiltnniserljRptoe.alioi2ivnNrcAve0eanmetsAn1lnhrhtl9utieeioc(l,mdlempewfiaFslrprleittiogRoolobvmdpunerNeaotrheaosanerAiasfntciotvni1)eltot,ei)xhcodnstwtaeherrihnlsroahe[lcadsc1firoes‐ce3etsxavhl]htcel.aoeuiercckpsrAeslrayoaeielenneemrntwnovecvbpeidttaatehelnascsfaetidetiectreicxoloeeplllmodelnr(siassofvsahowrnphjeooocmdraoawomressrercdmtrstm2atieahoitnsklrcoaneepeoessbfaotdnonteenoncfitrpsaoneedftcliluhtneasnolhsneccivte-nesecosbereste(rtoirifhicoyctmnreriehnoctet1maamihetp9eltmxaiu9dioot2ce6nRshnnserooNuatsextmicnfpomAccoegseoermtuoiloernfilamlrnpamgeeancetlesndeidtorpsoedseronwncecimconntiaotapndihcs1nfcitesae9ratclbhonn9tilenso6eRetr2.tNc6aAe0iAnln0l cell dsiusrcfoavceerryetcheapttosrtismtruilgagteiornedofincderutcaiibnleceelxl ossuormfaecesreeccreeptitoonrsintrimggasetrecdelilns,dcuyctiobtloexeicxoTsolymmepshecorceyttieosn(iCnTL), helper T lymphocytes (Th) and B lymphocytes (reviewed in [14]) These exosomes have an important role in intercellular communication during crucial immune effector responses such as antigen presentation and apoptosis [14]. In this context, a major contribution was to formally demonstrate that inducible Th and B lymphocyte exosome secretion occurred in a polarized manner at the IS between Th lymphocytes and APC [15] or B and Th lymphocytes [16], early studies of target cell-CTL synapses pointed out in this direction [17]. Taking into account these milestones and facts, exosomes have been extensively studied as biological vehicles for intercellular communication in several physiological and pathological circumstances, and constitute promising biomarkers for both diagnosis and prognosis in several relevant pathologies
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