PD-1+ Tcf1+ CD8+ T cells from established chronic infection can form memory while retaining a stableimprint of persistent antigen exposure

Mélanie Charmoy; Tania Wyss; Mauro Delorenzi; Werner Held

doi:10.1016/j.celrep.2021.109672

PD-1⁺ Tcf1⁺ CD8⁺ T cells from established chronic infection can form memory while retaining a stableimprint of persistent antigen exposure

Cell Rep. 2021 Sep 7;36(10):109672. doi: 10.1016/j.celrep.2021.109672.

Authors

Mélanie Charmoy¹, Tania Wyss², Mauro Delorenzi³, Werner Held⁴

Affiliations

¹ Department of Oncology, University of Lausanne, Lausanne, Switzerland.
² SIB Swiss Institute of Bioinformatics, Bioinformatics Core Facility, Lausanne, Switzerland.
³ Department of Oncology, University of Lausanne, Lausanne, Switzerland; SIB Swiss Institute of Bioinformatics, Bioinformatics Core Facility, Lausanne, Switzerland.
⁴ Department of Oncology, University of Lausanne, Lausanne, Switzerland. Electronic address: [email protected].

PMID: 34496259
DOI: 10.1016/j.celrep.2021.109672

Abstract

Virus-specific PD1⁺ Tcf1⁺ memory-like CD8⁺ T cells (T_MLs) maintain the CD8⁺ T cell response during chronic viral infection. However, the fate of these cells following cessation of persistent antigen exposure has been unclear. Here, we find that T_MLs persist upon transfer into antigen-free hosts and form memory following recall stimulation. Phenotypic, functional, and transcriptome analyses show that T_ML-derived memory cells resemble those arising in response to acute, resolved infection, but they retain features of chronically stimulated cells, including elevated PD-1 and Tox and reduced cytokine expression. This chronic infection imprint is largely accounted for by constitutive Tox expression. Virus-specific Tcf1⁺ CD8⁺ T cells that persist after clearance of systemic infection also display a chronic infection imprint. Notwithstanding, renewed virus exposure induces a recall response, which controls virus infection in part. Thus, cessation of chronic antigen exposure yields a memory CD8⁺ T cell compartment that reflects prior stimulation.

Keywords: CD8(+) T cells; Tcf1; Tcf7; Tox; acute resolved LCMV infection; cell fate; chronic LCMV infection; chronic stimulation imprint; memory formation; memory-like; progenitor-exhausted.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD8-Positive T-Lymphocytes / immunology*
Gene Expression Profiling / methods
Immunologic Memory / immunology*
Lymphocytic Choriomeningitis / immunology
Lymphocytic Choriomeningitis / virology*
Lymphocytic choriomeningitis virus / immunology
Lymphocytic choriomeningitis virus / pathogenicity*
Mice
Mice, Inbred C57BL
Persistent Infection / immunology
Persistent Infection / virology*
T Cell Transcription Factor 1 / immunology

Substances

T Cell Transcription Factor 1
TCF7 protein, human