CD4+FoxP3+ T regulatory cells subsets release small extracellular vesicles containing cell death-related proteins as potential mechanism of T cell suppression.

Introduction: T regulatory cells (Tregs) are pivotal for immune tolerance. Among the suppression mechanisms attributed to Tregs, the release of small extracellular vesicles (sEV) has been proposed with CD73, Nrp1 and the transfer of key miRNAs playing a key role. Although these findings have been described for natural Tregs (nTregs), little is known on Tregs induced Methods: Here, we characterized sEV production from three types of Tregs: nTregs and Results: Characterization of sEV production indicates that all Tregs produce sEV with similar size and presence of Alix and Tsg101, with RATregs showing the highest production of sEV. Regarding sEV function, nTregs, iTregs and RATregs produce sEV that suppress CD4+ T and CD8+ T cell proliferation. Interestingly, Discussion: Although this study does not explain the enhanced cell death observed in cultures with sEV produced by nTregs and RATregs, it does demonstrate that Tregs subsets produce sEV with inhibitory function driven -at least- by cell death, providing new insights on the biology of Tregs.