Application of T cell microvilli-derived particles generated by cholesterol chelation, as a vector for delivering molecule

Abstract

T cell surface is covered with abundant of finger-like microvilli and T cell receptors are clustered at that microvilli tip. And T cell microvilli particles (TMPs) are generated upon TCR stimulation and TMPs can deliver the messages of T cells to recipient cells. Based on the previous studies which demonstrated that cell microvilli particles are released by cholesterol chelating, we isolated T cell microvilli particles using a cholesterol chelating agent, Methyl-β-cyclodextrin (MβCD). In this study, we treated MβCD to T cells and observed surface microvilli formation and T cell surface molecule downregulation. In addition, we purified the cTMPs and treated to recipient cell, like dendritic cells (DCs), Jurkat T cells, and hRaji B cells. We found that cTMPs can activate the DCs in a dose dependent manner, and can deliver the T cell molecules to recipient cells regardless of cell type or origin species. And that molecules stably retained on the cell surface over time. Consistent with this potential role, cTMPs generated from CAR-T cells can mediate CAR molecule transfer and transferred CAR molecules can operate in recipient normal T cells. Thus, cTMPs may serve as a vector for delivering T cell molecules to other cells. Further studies about applications of cTMPs may permit their therapeutic exploitation in CAR-T cell therapy field.