ER-associated degradation adapter Sel1L is required for CD8+ T cell function and memory formation following acute viral infection.
Cell Rep
; 43(5): 114156, 2024 May 28.
Article
in En
| MEDLINE
| ID: mdl-38687642
ABSTRACT
The maintenance of antigen-specific CD8+ T cells underlies the efficacy of vaccines and immunotherapies. Pathways contributing to CD8+ T cell loss are not completely understood. Uncovering the pathways underlying the limited persistence of CD8+ T cells would be of significant benefit for developing novel strategies of promoting T cell persistence. Here, we demonstrate that murine CD8+ T cells experience endoplasmic reticulum (ER) stress following activation and that the ER-associated degradation (ERAD) adapter Sel1L is induced in activated CD8+ T cells. Sel1L loss limits CD8+ T cell function and memory formation following acute viral infection. Mechanistically, Sel1L is required for optimal bioenergetics and c-Myc expression. Finally, we demonstrate that human CD8+ T cells experience ER stress upon activation and that ER stress is negatively associated with improved T cell functionality in T cell-redirecting therapies. Together, these results demonstrate that ER stress and ERAD are important regulators of T cell function and persistence.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
CD8-Positive T-Lymphocytes
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Endoplasmic Reticulum-Associated Degradation
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Endoplasmic Reticulum Stress
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Immunologic Memory
Limits:
Animals
/
Female
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Humans
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Male
Language:
En
Journal:
Cell Rep
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos