Gene

Lymphocytic choriomeningitis

CXCL10

Cell biology

Biology

Chemokine

Virology

T cell

Stem cell

CXCR3

Chronic infection

CCL5

Immunology

Genetics

Progenitor cell

Immune system

In vitro

Inflammation

Cytotoxic T cell

IL-2 receptor

Chemokine receptor

Cellular differentiation

Immunity

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.

CXCL10 chemokine regulates heterogeneity of the CD8+ T cell response and viral set point during chronic infection