Dynamic adoption of anergy by antigen-exhausted CD4+ T cells.
Cell Rep
; 34(6): 108748, 2021 02 09.
Article
em En
| MEDLINE
| ID: mdl-33567282
ABSTRACT
Exhausted immune responses to chronic diseases represent a major challenge to global health. We study CD4+ T cells in a mouse model with regulatable antigen presentation. When the cells are driven through the effector phase and are then exposed to different levels of persistent antigen, they lose their T helper 1 (Th1) functions, upregulate exhaustion markers, resemble naturally anergic cells, and modulate their MAPK, mTORC1, and Ca2+/calcineurin signaling pathways with increasing dose and time. They also become unable to help B cells and, at the highest dose, undergo apoptosis. Transcriptomic analyses show the dynamic adjustment of gene expression and the accumulation of T cell receptor (TCR) signals over a period of weeks. Upon antigen removal, the cells recover their functionality while losing exhaustion and anergy markers. Our data suggest an adjustable response of CD4+ T cells to different levels of persisting antigen and contribute to a better understanding of chronic disease.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
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Anergia Clonal
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Células Th1
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Sinalização do Cálcio
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Sistema de Sinalização das MAP Quinases
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Antígenos
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article