Single-cell transcriptome analysis of CD8 + T-cell memory inflation

CD8 + T 细胞记忆膨胀的单细胞转录组分析

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作者: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 #

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.

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.

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 (T RM) 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.

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