Abstract
Activated T lymphocytes release vesicles, termed exosomes, enriched in cholesterol and exposing phosphatidylserine (PS) at their outer membrane leaflet. Although CD4+ activated T lymphocytes infiltrate an atherosclerotic plaque, the effects of T cell exosomes on the atheroma‐associated cells are not known. We report here that exosomes isolated from the supernatants of activated human CD4+ T cells enhance cholesterol accumulation in cultured human monocytes and THP‐1 cells. Lipid droplets found in the cytosol of exosome‐treated monocytes contained both cholesterol ester and free cholesterol. Anti‐phosphatidylserine receptor antibodies recognized surface protein on the monocyte plasma membrane and prevented exosome‐induced cholesterol accumulation, indicating that exosome internalization is mediated via endogenous phosphatidylserine receptor. The production of proinflammatory cytokine TNF‐α enhanced in parallel with monocyte cholesterol accumulation. Our data strongly indicate that exosomes released by activated T cells may represent a powerful, previously unknown, atherogenic factor. J. Cell. Physiol. 212: 174–181, 2007. © 2007 Wiley‐Liss, Inc.