Maintenance of PD-1 on brain-resident memory CD8 T cells is antigen independent

Shwetank, Hossam A. Abdelsamed, Elizabeth L. Frost, Heather M. Schmitz, Taryn E. Mockus, Ben A. Youngblood, Aron E. Lukacher

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Infection of the central nervous system (CNS) by murine polyomavirus (MuPyV), a persistent natural mouse pathogen, establishes brain-resident memory CD8 T cells (bT RM) that uniformly and chronically express programmed cell death protein 1 (PD-1) irrespective of the expression of α E integrin CD103, a T RM cell marker. In contrast, memory antiviral CD8 T cells in the spleen are PD-1 -, despite viral loads being similar in both the brain and spleen during persistent infection. Repetitive antigen engagement is central to sustained PD-1 expression by T cells in chronic viral infections; however, recent evidence indicates that expression of inhibitory receptors, including PD-1, is part of the T RM differentiation program. Here we asked whether PD-1 expression by CD8 bT RM cells during persistent MuPyV encephalitis is antigen dependent. By transferring MuPyV-specific CD8 bT RM cells into the brains of naive mice and mice infected with cognate epitope-sufficient and -deficient MuPyVs, we demonstrate that antigen and inflammation are dispensable for PD-1 maintenance. In vitro and direct ex vivo analyses indicate that CD103 - MuPyV-specific CD8 bT RM retain functional competence. We further show that the Pdcd-1 promoter of anti-MuPyV bT RM cells is epigenetically fixed in a demethylated state in the brain. In contrast, the PD-1 promoter of splenic antiviral memory CD8 T cells undergoes remethylation after being demethylated during acute infection. These data show that PD-1 expression is an intrinsic property of brain T RM cells in a persistent CNS viral infection.

Original languageEnglish (US)
Pages (from-to)953-959
Number of pages7
JournalImmunology and Cell Biology
Volume95
Issue number10
DOIs
StatePublished - Nov 1 2017

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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