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Chronic viral infection alters PD-1 locus subnuclear localization in cytotoxic CD8 + T cells.
- Source :
-
Cell reports [Cell Rep] 2024 Aug 27; Vol. 43 (8), pp. 114547. Date of Electronic Publication: 2024 Jul 30. - Publication Year :
- 2024
-
Abstract
- During chronic infection, virus-specific CD8 <superscript>+</superscript> cytotoxic T lymphocytes (CTLs) progressively lose their ability to mount effective antiviral responses. This "exhaustion" is coupled to persistent upregulation of inhibitory receptor programmed death-1 (PD-1) (Pdcd1)-key in suppressing antiviral CTL responses. Here, we investigate allelic Pdcd1 subnuclear localization and transcription during acute and chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. Pdcd1 alleles dissociate from transcriptionally repressive chromatin domains (lamin B) in virus-specific exhausted CTLs but not in naive or effector CTLs. Relative to naive CTLs, nuclear positioning and Pdcd1-lamina dissociation in exhausted CTLs reflect loss of Pdcd1 promoter methylation and greater PD-1 upregulation, although a direct correlation is not observed in effector cells, 8 days post-infection. Genetic deletion of B lymphocyte-induced maturation protein 1 (Blimp-1) enhances Pdcd1-lamina dissociation in effector CTLs, suggesting that Blimp-1 contributes to maintaining Pdcd1 localization to repressive lamina. Our results identify mechanisms governing Pdcd1 subnuclear localization and the broader role of chromatin dynamics in T cell exhaustion.<br />Competing Interests: Declaration of interests Catarina Sacristán is an employee of Cell Press, Elsevier, but was uninformed of manuscript handling. Peer review was fully independent of said author.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Mice
Cell Nucleus metabolism
Positive Regulatory Domain I-Binding Factor 1 metabolism
Positive Regulatory Domain I-Binding Factor 1 genetics
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Chronic Disease
Promoter Regions, Genetic genetics
Genetic Loci
Programmed Cell Death 1 Receptor metabolism
Programmed Cell Death 1 Receptor genetics
Lymphocytic choriomeningitis virus immunology
Lymphocytic Choriomeningitis immunology
Lymphocytic Choriomeningitis virology
Mice, Inbred C57BL
T-Lymphocytes, Cytotoxic immunology
T-Lymphocytes, Cytotoxic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 43
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 39083377
- Full Text :
- https://doi.org/10.1016/j.celrep.2024.114547