Clonally Expanded Virus-Specific CD8 T Cells Acquire Diverse Transcriptional Phenotypes During Acute, Chronic, and Latent Infections.

Autor:	Kuhn R; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Sandu I; Institute of Microbiology, ETH Zurich, Zurich, Switzerland., Agrafiotis A; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Hong KL; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Shlesinger D; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Neimeier D; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Merkler D; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.; Division of Clinical Pathology, Geneva University Hospital, Geneva, Switzerland., Oxenius A; Institute of Microbiology, ETH Zurich, Zurich, Switzerland., Reddy ST; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Yermanos A; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.; Institute of Microbiology, ETH Zurich, Zurich, Switzerland.; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Feb 02; Vol. 13, pp. 782441. Date of Electronic Publication: 2022 Feb 02 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.782441
Abstrakt:	CD8+ T cells play a crucial role in the control and resolution of viral infections and can adopt a wide range of phenotypes and effector functions depending on the inflammatory context and the duration and extent of antigen exposure. Similarly, viral infections can exert diverse selective pressures on populations of clonally related T cells. Technical limitations have nevertheless made it challenging to investigate the relationship between clonal selection and transcriptional phenotypes of virus-specific T cells. We therefore performed single-cell T cell receptor (TCR) repertoire and transcriptome sequencing of virus-specific CD8 T cells in murine models of acute, chronic and latent infection. We observed clear infection-specific populations corresponding to memory, effector, exhausted, and inflationary phenotypes. We further uncovered a mouse-specific and polyclonal T cell response, despite all T cells sharing specificity to a single viral epitope, which was accompanied by stereotypic TCR germline gene usage in all three infection types. Persistent antigen exposure during chronic and latent viral infections resulted in a higher proportion of clonally expanded T cells relative to acute infection. We furthermore observed a relationship between transcriptional heterogeneity and clonal expansion for all three infections, with highly expanded clones having distinct transcriptional phenotypes relative to less expanded clones. Together our work relates clonal selection to gene expression in the context of viral infection and further provides a dataset and accompanying software for the immunological community. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Kuhn, Sandu, Agrafiotis, Hong, Shlesinger, Neimeier, Merkler, Oxenius, Reddy and Yermanos.)
Databáze:	MEDLINE
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