Abstract
CD8+ T cells responding to chronic infection adapt an altered differentiation program that provides some restraint on pathogen replication yet limits immunopathology. This adaptation is imprinted in stem-like cells and propagated to their progeny. Understanding the molecular control of CD8+ T cell differentiation in chronic infection has important therapeutic implications. Here, we find that the chemokine receptor CXCR3 is highly expressed on viral-specific stem-like CD8+ T cells and that one of its ligands, CXCL10, regulates the persistence and heterogeneity of responding CD8+ T cells in spleens of mice chronically infected with lymphocytic choriomeningitis virus. CXCL10 is produced by inflammatory monocytes and fibroblasts of the splenic red pulp, where it grants stem-like cells access to signals promoting differentiation and limits their exposure to pro-survival niches in the white pulp. Consequently, functional CD8+ T cell responses are greater in Cxcl10−/− mice and are associated with a lower viral set point.
Original language | English (US) |
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Pages (from-to) | 82-97.e8 |
Journal | Immunity |
Volume | 55 |
Issue number | 1 |
DOIs | |
State | Published - Jan 11 2022 |
Keywords
- CD8+ T cells
- CXCL10
- CXCR3
- LCMV
- T cell differentiation
- T cell exhaustion
- TCF-1
- chemokine
- chronic viral infection
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases