期刊
CELL REPORTS
卷 13, 期 8, 页码 1578-1588出版社
CELL PRESS
DOI: 10.1016/j.celrep.2015.10.034
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资金
- Oxford Martin School
- Wellcome Trust [WT091663MA]
- Swiss National Science Foundation
- Schweizerische Stiftung fur Medizinisch-Biologische Stipendien (SSMBS)
- NIH [U19AI082630]
- MRC
- NIHR Biomedical Research Centre, Oxford
- Medical Research Council [1890672, G0701694, MR/K010239/1] Funding Source: researchfish
- National Institute for Health Research [CL-2013-18-009, NF-SI-0510-10204] Funding Source: researchfish
- MRC [MR/K010239/1, G0701694] Funding Source: UKRI
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.
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