CXCL10 Chemokine Regulates Heterogeneity of the CD8+ T Cell Response and Viral Set Point During Chronic Infection

Authors

Aleksandra J Ozga
Melvyn T Chow
Mateus E Lopes
Rachel L Servis
Mauro Di Pilato
Philippe Dehio
Jeffrey Lian
Thorsten R Mempel
Andrew D Luster

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