Adenoviral Vector Vaccination Induces a Conserved Program of CD8(+) T Cell Memory Differentiation in Mouse and Man

作者：Bolinger Beatrice^*; Sims Stuart; Swadling Leo; O'Hara Geraldine; de Lara Catherine; Baban Dilair; Saghal Natasha; Lee Lian Ni; Marchi Emanuele; Davis Mark; Newell Evan; Capone Stefania; Folgori Antonella; Barnes Ellie; Klenerman Paul

来源：Cell Reports, 2015, 13(8): 1578-1588.

DOI：10.1016/j.celrep.2015.10.034

Following exposure to vaccines, antigen-specific CD8(+) T cell responses develop as long-term memory pools. Vaccine strategies based on adenoviral vectors, e.g., those developed for HCV, are able to induce and sustain substantial CD8(+) T cell populations. How such populations evolve following vaccination remains to be defined at a transcriptional level. We addressed the transcriptional regulation of divergent CD8(+) T cell memory pools induced by an adenovector encoding a model antigen (beta-galactosidase). We observe transcriptional profiles that mimic those following infection with persistent pathogens, murine and human cytomegalovirus (CMV). Key transcriptional hallmarks include upregulation of homing receptors and anti-apoptotic pathways, driven by conserved networks of transcription factors, including T-bet. In humans, an adenovirus vaccine induced similar CMV-like phenotypes and transcription factor regulation. These data clarify the core features of CD8(+) T cell memory following vaccination with adenovectors and indicate a conserved pathway for memory development shared with persistent herpesviruses.

• 出版日期2015-11-24