Cell Reports (Aug 2020)

Landscape of Exhausted Virus-Specific CD8 T Cells in Chronic LCMV Infection

  • Ioana Sandu,
  • Dario Cerletti,
  • Nathalie Oetiker,
  • Mariana Borsa,
  • Franziska Wagen,
  • Ilaria Spadafora,
  • Suzanne P.M. Welten,
  • Ugne Stolz,
  • Annette Oxenius,
  • Manfred Claassen

Journal volume & issue
Vol. 32, no. 8
p. 108078

Abstract

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Summary: A hallmark of chronic infections is the presence of exhausted CD8 T cells, characterized by a distinct transcriptional program compared with functional effector or memory cells, co-expression of multiple inhibitory receptors, and impaired effector function, mainly driven by recurrent T cell receptor engagement. In the context of chronic lymphocytic choriomeningitis virus (LCMV) infection in mice, most studies focused on studying splenic virus-specific CD8 T cells. Here, we provide a detailed characterization of exhausted CD8 T cells isolated from six different tissues during established LCMV infection, using single-cell RNA sequencing. Our data reveal that exhausted cells are heterogeneous, adopt organ-specific transcriptomic profiles, and can be divided into five main functional subpopulations: advanced exhaustion, effector-like, intermediate, proliferating, or memory-like. Adoptive transfer experiments showed that these phenotypes are plastic, suggesting that the tissue microenvironment has a major impact in shaping the phenotype and function of virus-specific CD8 T cells during chronic infection.

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