Title

Exosomes as endogenous adjuvants

Date of Completion

January 2007

Keywords

Health Sciences, Immunology

Degree

Ph.D.

Abstract

Exosomes are microscopic vesicular structures released by many different cell types. This dissertation presents the results of experiments that characterize, on both molecular and structural levels, exosomes isolated from murine tumor cell lines. Moreover, it presents evidence that exosomes induce the phenotypic and functional maturation of dendritic cells. This result is exciting, as it adds exosomes to a short list of endogenous adjuvants identified so far, including heat shock proteins, uric acid, and DNA. However, unlike the previously identified endogenous adjuvants, exosomes are released by living cells and, therefore, may be the first identified mechanism by which a live cell can signal the immune system to become activated. In addition, this dissertation provides preliminary evidence that exosomes, like the heat shock proteins contained within them, are efficient mediators of cross-presentation in vivo. If the heat shock proteins within exosomes are responsible for the cross-presentation, they are approximately 200 times more potent when contained within exosomes than when delivered as soluble protein. ^