Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
06 06 2022
06 06 2022
Historique:
received:
20
10
2021
revised:
04
01
2022
accepted:
08
03
2022
entrez:
23
5
2022
pubmed:
24
5
2022
medline:
26
5
2022
Statut:
ppublish
Résumé
Transcription factors ThPOK and Runx3 regulate the differentiation of "helper" CD4+ and "cytotoxic" CD8+ T cell lineages respectively, inducing single positive (SP) T cells that enter the periphery with the expression of either the CD4 or CD8 co-receptor. Despite the expectation that these cell fates are mutually exclusive and that mature CD4+CD8+ double positive (DP) T cells are present in healthy individuals and augmented in the context of disease, yet their molecular features and pathophysiologic role are disputed. Here, we show DP T cells in murine and human tumors as a heterogenous population originating from SP T cells which re-express the opposite co-receptor and acquire features of the opposite cell type's phenotype and function following TCR stimulation. We identified distinct clonally expanded DP T cells in human melanoma and lung cancer by scRNA sequencing and demonstrated their tumor reactivity in cytotoxicity assays. Our findings indicate that antigen stimulation induces SP T cells to differentiate into DP T cell subsets gaining in polyfunctional characteristics.
Identifiants
pubmed: 35604411
pii: 213237
doi: 10.1084/jem.20212169
pmc: PMC9130031
pii:
doi:
Substances chimiques
CD4 Antigens
0
CD8 Antigens
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : T32 CA009110
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : Cancer Research Institute
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA056821
Pays : United States
Organisme : NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2022 Schad et al.
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