Title

The opposing immunological effects of double-stranded RNA on cytotoxic CD8 T cell response

Date of Completion

January 2010

Keywords

Biology, Cell|Health Sciences, Immunology

Degree

Ph.D.

Abstract

The cytotoxic CD8 T cells constitute an important compartment of the adaptive immune system that plays a critical role in anti-viral and tumor immunity. Induction of a robust CD8 T cell response requires provision of antigen as well as the presence of danger signals. Double-stranded RNA (dsRNA), a molecular moiety of many viruses, is one of the danger signals that can profoundly impact CD8 T cell activation, effector differentiation and survival as a memory cell pool that confers protection against future assault by pathogens. Therefore, synthetic dsRNA represents a promising candidate for vaccine development that boosts CD8 T cell responses. In this thesis, the mechanisms by which a synthetic dsRNA, poly(I:C), shapes CD8 T cell responses were investigated. We uncovered how poly(1:C) can both augment or dampen CD8 T cell responses, and how these opposite effects are fostered by other cell types and mediators of the immune system. Results presented here provide a mechanistic basis for fine-tuning CD8 T cell responses in therapeutic settings, and further our understanding of dsRNA response under physiological conditions. ^