Eomes cannot replace its paralog T-bet during expansion and differentiation of CD8 effector T cells.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
30
04
2020
accepted:
10
08
2020
revised:
09
10
2020
pubmed:
30
9
2020
medline:
13
11
2020
entrez:
29
9
2020
Statut:
epublish
Résumé
The two T-box transcription factors T-bet and Eomesodermin (Eomes) are important regulators of cytotoxic lymphocytes (CTLs), such as activated CD8 T cells, which are essential in the fight against intracellular pathogens and tumors. Both transcription factors share a great degree of homology based on sequence analysis and as a result exert partial functional redundancy during viral infection. However, the actual degree of redundancy between T-bet and Eomes remains a matter of debate and is further confounded by their distinct spatiotemporal expression pattern in activated CD8 T cells. To directly investigate the functional overlap of these transcription factors, we generated a new mouse model in which Eomes expression is under the transcriptional control of the endogenous Tbx21 (encoding for T-bet) locus. Applying this model, we demonstrate that the induction of Eomes in lieu of T-bet cannot rescue T-bet deficiency in CD8 T cells during acute lymphocytic choriomeningitis virus (LCMV) infection. We found that the expression of Eomes instead of T-bet was not sufficient for early cell expansion or effector cell differentiation. Finally, we show that imposed expression of Eomes after acute viral infection promotes some features of exhaustion but must act in concert with other factors during chronic viral infection to establish all hallmarks of exhaustion. In summary, our results clearly underline the importance of T-bet in guiding canonical CTL development during acute viral infections.
Identifiants
pubmed: 32991634
doi: 10.1371/journal.ppat.1008870
pii: PPATHOGENS-D-20-00887
pmc: PMC7546498
doi:
Substances chimiques
Eomes protein, mouse
0
Fetal Proteins
0
T-Box Domain Proteins
0
T-box transcription factor TBX21
0
Interferon-gamma
82115-62-6
Brachyury protein
EQ43SC3GDB
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008870Déclaration de conflit d'intérêts
I have read the journal's policy and the authors of this manuscript have the following competing interests: A.H. is now an employee of AstraZeneca, and may own stock or stock options.
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