%0 PDF %T The STING of death in T cells: IFN responses and cell death result from activation of T cell STING %A Larkin, Bridget. %D 2017-04-18T11:39:16.354Z %8 2017-04-18 %R http://localhost/files/bz60d780b %X Abstract: STING, a critical mediator of IFN-I responses, has increasingly been recognized for its importance in a variety of immune responses to intracellular bacterial and viral DNA as well as endogenous DNA involved in tumorigenesis and the development of autoimmune disease. Therapeutically, STING has also been proven to be a potent vaccine adjuvant for model and tumor antigens. Yet, in all of these contexts STING has primarily been studied for its role in innate immune activation of macrophages and dendritic cells. We present here the first evidence of STING activation in T cells, resulting in IFN-I production and increased ISG expression—responses that largely mirror the outcome of STING activation in innate cells. In addition, we identify T cell-specific responses to STING activation: unlike in macrophages and dendritic cells, T cells exhibit dramatic increases in cell stress response and proapoptotic pathways that ultimately result in cell death. These results may prompt a re-evaluation of the therapeutic uses of STING agonists, as they could cause unrecognized damage to the T cell compartment. Conversely, our findings suggest STING-based therapies may be beneficial for treating T cell lymphoproliferative disorders, T cell lymphomas, and T cell-based transplant rejection while sparing other immune system components.; Thesis (Ph.D.)--Tufts University, 2017.; Submitted to the Dept. of Immunology.; Advisor: Alexander Poltorak.; Committee: Stephen Bunnell, Brigitte Huber, and Henry Wortis.; Keyword: Immunology. %[ 2022-10-11 %9 Text %~ Tufts Digital Library %W Institution