Abstract

The Characterisation and Function of Exosomes Derived from Human T Regulatory Cells

Lesley Smyth, Senior Lecturer, University of East London

Regulatory T-cells (Tregs) maintain immune tolerance to self-antigens and prevent excessive pro-inflammatory actions of T-effectors (Teffs) and antigen presenting cells responses. In a murine setting, these cells inhibit the aforementioned cells in a variety of ways including the release of extracellular vesicles (EVs). Release of these vesicles plays a key role in the suppressive capability of murine Tregs through the expression of the ectoenzyme CD73 and specific miRNA species. We have now extended this observation to human CD4+CD25+127lo T-cells isolated from blood, and cultured in the presence of anti-CD3/CD28-coated beads, rapamyacin and IL-2. These cells were suppressive and display key molecules associated with regulation. Activated human Tregs released 50-100nm-sized EVs expressing CD63 and CD81 as well as CD25 and CD39. Excitingly, Treg Evs were capable of suppressing Teffs responses resulting in less activation and the production of an anti-inflammatory cytokine profile. Their suppressive capabilities were also evident in vivo. Adoptive transfer of Treg EVs prevented T cell infiltration and skin damage in a humanised model of transplantation. Our data highlights that human Tregs produce EVs following activation and that this is a novel mechanism by which human Tregs modify immune Teff responses in vivo.