New 'Cell Reports' study by the Oxenius Lab
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
Cell Rep. (2020) Aug 25;32(8):108078.
doi: 10.1016/j.celrep.2020.108078.
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.
The study by the Oxenius and Claassen groups at ETH provides a detailed characterization of exhausted CD8 T cells isolated from six different tissues during established LCMV infection.
Link to the paper in external page "Cell Reports"
Link to the D-BIOL news article