Single-cell transcriptome analysis of CD8+ T-cell memory inflation [version 1; peer review: 2 approved]

• Main Authors: Andrew J. Highton, Madeleine E. Zinser, Lian Ni Lee, Claire L. Hutchings, Catherine De Lara, Chansavath Phetsouphanh, Chris B. Willberg, Claire L. Gordon, Paul Klenerman, Emanuele Marchi
• Format: Article
• Language: English
• Published: Wellcome 2019-05-01
• Series: Wellcome Open Research
• Online Access: https://wellcomeopenresearch.org/articles/4-78/v1

Background: Persistent viruses such as murine cytomegalovirus (MCMV) and adenovirus-based vaccines induce strong, sustained CD8+ T-cell responses, described as memory “inflation”. These retain functionality, home to peripheral organs and are associated with a distinct transcriptional program. Methods: To further define the nature of the transcriptional mechanisms underpinning memory inflation at different sites we used single-cell RNA sequencing of tetramer-sorted cells from MCMV-infected mice, analyzing transcriptional networks in virus-specific populations in the spleen and gut intra-epithelial lymphocytes (IEL). Results: We provide a transcriptional map of T-cell memory and define a module of gene expression, which distinguishes memory inflation in spleen from resident memory T-cells (TRM) in the gut. Conclusions: These data indicate that CD8+ T-cell memory in the gut epithelium induced by persistent viruses and vaccines has a distinct quality from both conventional memory and “inflationary” memory which may be relevant to protection against mucosal infections.