Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T cells influence effector potential.
Cell Rep
; 37(9): 110064, 2021 11 30.
Article
in En
| MEDLINE
| ID: mdl-34852223
ABSTRACT
CD4+ T cells have a remarkable potential to differentiate into diverse effector lineages following activation. Here, we probe the heterogeneity present among naive CD4+ T cells before encountering their cognate antigen to ask whether their effector potential is modulated by pre-existing transcriptional and chromatin landscape differences. Single-cell RNA sequencing shows that key drivers of variability are genes involved in T cell receptor (TCR) signaling. Using CD5 expression as a readout of the strength of tonic TCR interactions with self-peptide MHC, and sorting on the ends of this self-reactivity spectrum, we find that pre-existing transcriptional differences among naive CD4+ T cells impact follicular helper T (TFH) cell versus non-TFH effector lineage choice. Moreover, our data implicate TCR signal strength during thymic development in establishing differences in naive CD4+ T cell chromatin landscapes that ultimately shape their effector potential.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromatin
/
Lymphocyte Activation
/
Receptors, Antigen, T-Cell
/
CD4-Positive T-Lymphocytes
/
Cell Differentiation
/
T-Lymphocytes, Helper-Inducer
/
Lymphocytic Choriomeningitis
Limits:
Animals
Language:
En
Journal:
Cell Rep
Year:
2021
Document type:
Article
Affiliation country:
Canada