The Role of Extracellular Vesicle and Tunneling Nanotube-Mediated Intercellular Cross-Talk Between Mesenchymal Stem Cells and Human Peripheral T Cells

The role of extracellular vesicles (EVs) in mediating the immunosuppressory properties of mesenchymal stem cells (MSCs) has recently attracted remarkable scientific interest. The aim of this work was to analyze the transport mechanisms of membrane and cytoplasmic components between T lymphocytes and adipose tissue-derived MSCs (AD-MSCs), by focusing on the role of distinct populations of EVs, direct cell-cell contacts, and the soluble mediators per se in modulating T lymphocyte function. We found that neither murine thymocytes and human primary T cells nor Jurkat lymphoblastoid cells incorporated appreciable amounts of MSC-derived microvesicles (MVs) or exosomes (EXOs). Moreover, these particles had no effect on the proliferation and IFN-gamma production of in vitro-stimulated primary T cells. In contrast, AD-MSCs incorporated large amounts of membrane components from T cells as an intensive uptake of EXOs and MVs could be observed. Interestingly, we found a bidirectional exchange of cytoplasmic components between human AD-MSCs and primary T lymphocytes, mediated by tunneling nanotubes (TNTs) derived exclusively from the T cells. In contrast, TNTs couldn't be observed between AD-MSCs and the Jurkat cells. Our results reveal a novel and efficient way of intercellular communication between MSCs and T cells, and may help a better understanding of the immunomodulatory function of MSCs.