CXCL10 chemokine regulates heterogeneity of the CD8+ T cell response and viral set point during chronic infection.
Immunity
; 55(1): 82-97.e8, 2022 01 11.
Article
in En
| MEDLINE
| ID: mdl-34847356
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Spleen
/
Monocytes
/
CD8-Positive T-Lymphocytes
/
Chemokine CXCL10
/
Receptors, CXCR3
/
Lymphocytic Choriomeningitis
/
Lymphocytic choriomeningitis virus
Limits:
Animals
Language:
En
Journal:
Immunity
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2022
Document type:
Article
Affiliation country: