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

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

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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 languageEnglish (US)
Pages (from-to)82-97.e8
JournalImmunity
Volume55
Issue number1
DOIs
StatePublished - 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

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