Direct exosome stimulation of peripheral humanT cells detected by ELISPOT.

Autor: Admyre, Charlotte, Johansson, Sara M., Paulie, Staffan, Gabrielsson, Susanne
Zdroj: European Journal of Immunology; Jul2006, Vol. 36 Issue 7, p1772-1781, 10p
Abstrakt: Exosomes from APC are nano-vesicles that can induce antigen-specific T cell responses and are presently explored as therapeutic tools in different clinical settings. Investigations of the capacity of exosomes to stimulate T cells in vitro have mostly been performed on T cell hybridomas, clones or lines. Whether exosomes can stimulate T cells directly or need the presence of dendritic cells (DC) is debated. We could detect exosome-induced antigen-specific CD8 T cell responses in peripheral blood from humans. Exosomes from monocyte-derived DC (MDDC) were loaded with a mix of 23 immunogenic peptides from EBV, CMV and influenza virus, and added to autologous peripheral CD8 T cells. IFN-γ-producing cells were detected by enzyme-linked immunospot assay (ELISPOT). MDDC-exosomes induced IFN-γ production in CD8 T cells without addition of DC. The response was exosome dose dependent, and dependent on exosomal MHC class I. Furthermore, we detected an enhanced T cell stimulatory capacity by exosomes from lipopolysaccharide-matured MDDC compared to exosomes from immature MDDC. Exosomes could also induce TNF-α production. These results show, for the first time, that exosomes can directly stimulate human peripheral CD8 T cells in an antigen-specific manner and that ELISPOT is a suitable method for detecting exosome-induced peripheral T cell responses. This system may provide a useful tool when developing exosomes as therapeutic agents. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index