Landscape of exhausted virus-specific CD8 T cells in chronic LCMV infection
Chronic infections lead to the development of exhausted CD8 T cells. A recent ‘Cell Reports’ study by the Oxenius (IMB) and Claassen groups (IMSB) provides a detailed characterization of exhausted CD8 T cells isolated from six different tissues during established LCMV infection.
A hallmark of chronic infections is the overstimulation of CD8 T cells leading to exhaustion, characterized by a distinct transcriptional program compared to functional effector or memory cells. In the context of chronic Lymphocytic Choriomeningitis virus (LCMV) infection in mice, most studies focused on studying splenic virus-specific CD8 T cells. The Oxenius and Claassen groups generated an atlas of exhausted CD8 T cells isolated from six different tissues during established LCMV infection, using single-cell RNA sequencing. These data reveal that exhausted cells are heterogeneous and adopt organ-specific profiles, and can be divided into five main functional subpopulations: advanced exhaustion, effector-like, intermediate, proliferating, or memory-like. In vivo antibody labeling showed that cells belonging to these subpopulations are differentially positioned in these tissues, with effector-like and intermediate phenotype cells being close to the vasculature and memory-like and more exhausted cells residing deeper in the tissue. 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.
Link to the paper in external page "Cell Reports".