Exosomes represent a novel mechanism of regulatory T cell suppression (P1079)

Regulatory T cells suppress via a variety of mechanisms, both contact-dependent and -independent mechanisms. These is some controversy as to which mechanisms play more dominant roles during various disease states as well as maintenance of immune homeostasis. Our laboratory has found that regulatory T cells secrete exosome-like vesicles that are 20 to 50 nm in diameter. Membrane vesicles have been shown to mediate communication amongst immune cells, but they also mediate communication between immune cells and cancer cells and between and immune cells and pathogens. Membrane vesicles mediate physiologic changes in recipient cells by initiating cellular signaling events following receptor binding, or via uptake and integration of vesicular cargo, which can include receptors, enzymes, cytokines, chemokines and genetic material. We have found that functional regulatory T cell membrane vesicles mediate suppression of conventional CD4+ T cells, whereas resting regulatory T cell and conventional T cell vesicles do not. Furthermore, we have found that 293F cells package overexpressed immunosuppressive cytokines into exosomes following transfection. Taken together these data suggest that exosome-like vesicles represent a bridge between contact dependent and independent regulatory T cell suppression.