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 Lukacher

Research output: Contribution to journalArticle

20 Citations (Scopus)

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

Fingerprint

Polyomavirus
Maintenance
Programmed Cell Death 1 Receptor
T-Lymphocytes
Antigens
Brain
Antiviral Agents
Central Nervous System Viral Diseases
Spleen
Central Nervous System Infections
Virus Diseases
Encephalitis
Infection
Viral Load
Integrins
Mental Competency
Epitopes
Inflammation

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

Shwetank, Abdelsamed, H. A., Frost, E. L., Schmitz, H. M., Mockus, T. E., Youngblood, B. A., & Lukacher, A. (2017). Maintenance of PD-1 on brain-resident memory CD8 T cells is antigen independent. Immunology and Cell Biology, 95(10), 953-959. https://doi.org/10.1038/icb.2017.62
Shwetank ; Abdelsamed, Hossam A. ; Frost, Elizabeth L. ; Schmitz, Heather M. ; Mockus, Taryn E. ; Youngblood, Ben A. ; Lukacher, Aron. / Maintenance of PD-1 on brain-resident memory CD8 T cells is antigen independent. In: Immunology and Cell Biology. 2017 ; Vol. 95, No. 10. pp. 953-959.
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Shwetank, Abdelsamed, HA, Frost, EL, Schmitz, HM, Mockus, TE, Youngblood, BA & Lukacher, A 2017, 'Maintenance of PD-1 on brain-resident memory CD8 T cells is antigen independent', Immunology and Cell Biology, vol. 95, no. 10, pp. 953-959. https://doi.org/10.1038/icb.2017.62

Maintenance of PD-1 on brain-resident memory CD8 T cells is antigen independent. / Shwetank; Abdelsamed, Hossam A.; Frost, Elizabeth L.; Schmitz, Heather M.; Mockus, Taryn E.; Youngblood, Ben A.; Lukacher, Aron.

In: Immunology and Cell Biology, Vol. 95, No. 10, 01.11.2017, p. 953-959.

Research output: Contribution to journalArticle

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Shwetank, Abdelsamed HA, Frost EL, Schmitz HM, Mockus TE, Youngblood BA et al. Maintenance of PD-1 on brain-resident memory CD8 T cells is antigen independent. Immunology and Cell Biology. 2017 Nov 1;95(10):953-959. https://doi.org/10.1038/icb.2017.62