In clinical studies, it has been demonstrated that endothelial EVs (Annexin V+, CD31/PECAM-1+) obtained from serum of HC were involved in the activation of CD4+ and CD8+ T-lymphocytes through expression of b2-microglobulin, MHC II, CD40, and inducible T cell costimulator ligand (ICOSL) [43], while endothelial EVs, isolated from the serum of active RRMS patients, were able to also promote the trans-endothelial migration of monocytes through a monolayer model of BBB. This evidence concerns the gene ICOSLG and relapsing-remitting multiple sclerosis.