B7-H1 influences the accumulation of virus-specific tissue resident memory T cells in the central nervous system

Kevin D. Pavelko, Michael P. Bell, Susan M. Harrington, Haidong M Dong

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Therapies that target the PD-1/B7-H1 axis have revolutionized cancer treatment, yet precise knowledge of how this pathway provides benefit continues to evolve. Here, we report a novel role for the immune checkpoint ligand B7-H1 in the accumulation of tissue-resident memory CD8+ T-cells (TRM). After intracranial infection, Theiler's murine encephalomyelitis virus (TMEV) generates TRM that are maintained in the central nervous system (CNS) tissues of B7-H1WT animals. Although no differences in acute T-cell responses between B7-H1WT and B7-H1KO are observed, at long-term periods post-infection the maintenance of CD8+ TRM is diminished in B7-H1KO animals. This is accompanied by redistribution of the resident CD8+ population from primarily CD103+ TRM to a diminished population of TRM and a preponderance of non-specified PD-1+ CD103- CD8+ T-cells. T-cell transfer studies demonstrate that host B7-H1 is necessary for maintaining TRM and limiting accumulation of PD-1+ CD103- CD8+ T-cells. The lack of host B7-H1 results in compromised control of a heterologous virus re-challenge demonstrating a functional defect in TRM mediated virus control. This study reveals a new role for B7-H1 in TRM and pro-inflammatory PD-1+ CD103- CD8+ T-cell accumulation in the CNS and gives insight for using B7-H1/PD-1 blockade in modulating long-term T-cell protection.

Original languageEnglish (US)
Article number1532
JournalFrontiers in Immunology
Volume8
Issue numberNOV
DOIs
StatePublished - Nov 9 2017

Keywords

  • B7-H1
  • CD8
  • CTL
  • Immune checkpoint
  • Picornaviruses
  • Programmed death-1
  • Theiler's murine encephalomyelitis virus
  • Tissue resident memory
  • Viruses

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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