
Faculty, Staff and Student Publications
Publication Date
1-11-2022
Journal
Immunity
Abstract
CD8+ T cells responding to chronic infection adapt an altered differentiation program that provides some restrain 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 found that the chemokine receptor CXCR3 was highly expressed on viral-specific stem-like CD8+ T cells and that one of its ligands, CXCL10, regulated the persistence and heterogeneity of responding CD8+ T cells in spleens of mice chronically infected with lymphocytic choriomeningitis virus. CXCL10 was produced by inflammatory monocytes and fibroblasts of the splenic red pulp where it granted stem-like cells access to signals promoting differentiation and limited their exposure to pro-survival niches in the white pulp. Consequently, functional CD8+ T cell responses were greater in Cxcl10−/− mice and were associated with a lower viral set point.
Keywords
Animals, B7-H1 Antigen, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Proliferation, Cell Self Renewal, Chemokine CXCL10, Chronic Disease, Clonal Selection, Antigen-Mediated, Female, Hepatocyte Nuclear Factor 1-alpha, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Mice, Mice, Inbred C57BL, Mice, Knockout, Monocytes, Receptors, CXCR3, Spleen, CD8 T cell differentiation, CXCR3, CXCL10, LCMV, chronic viral infection, chemokine
DOI
10.1016/j.immuni.2021.11.002
PMID
34847356
PMCID
PMC8755631
PubMedCentral® Posted Date
1-11-2023
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons