The Immune Memory Response and Metabolic Requirements of Human Gamma Delta T Cells

Abstract

γδ T cells are unconventional T cells that can mediate pro-inflammatory, cytotoxic, phagocytotic and professional antigen presenting properties. Sharing the features of both adaptive and innate immunity, γδ T cells also showed signs of induction of both adaptive immune memory and innate immune memory responses. These multi-functional cells therefore play indispensable roles in acquired immunity, host defense against infection and immune surveillance against cancer. In the first part of this thesis, I reviewed the concept and recent advances of innate immune memory and showed the discovery of the trained immunity phenotype in γδ T cells by BCG and MMR vaccination, demonstrating for the first time that γδ T cells can mount both adaptive and innate memory. In the second part of the thesis, I focused on investigating the effect of manipulating mevalonate metabolism on the immune function of γδ T cells as well as the metabolic and immune functional changes of γδ T cells in autoinflammatory and immunodeficient disorders. The result of these studies encouraged us to take into account the adverse effects of mevalonate pathway inhibitors on gd T cells and provided possible reasons for the limited effectiveness and efficiency of the current γδ T cellbased therapy. Altogether, my thesis offered additional knowledge to facilitate the development of next-generation vaccines and a better γδ T cell-based therapy for cancer and infectious diseases in the future.