Rethinking peripheral T cell tolerance: checkpoints across a T cell's journey.
Journal
Nature reviews. Immunology
ISSN: 1474-1741
Titre abrégé: Nat Rev Immunol
Pays: England
ID NLM: 101124169
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
accepted:
18
09
2020
pubmed:
21
10
2020
medline:
11
5
2021
entrez:
20
10
2020
Statut:
ppublish
Résumé
Following their exit from the thymus, T cells are endowed with potent effector functions but must spare host tissue from harm. The fate of these cells is dictated by a series of checkpoints that regulate the quality and magnitude of T cell-mediated immunity, known as tolerance checkpoints. In this Perspective, we discuss the mediators and networks that control the six main peripheral tolerance checkpoints throughout the life of a T cell: quiescence, ignorance, anergy, exhaustion, senescence and death. At the naive T cell stage, two intrinsic checkpoints that actively maintain tolerance are quiescence and ignorance. In the presence of co-stimulation-deficient T cell activation, anergy is a dominant hallmark that mandates T cell unresponsiveness. When T cells are successfully stimulated and reach the effector stage, exhaustion and senescence can limit excessive inflammation and prevent immunopathology. At every stage of the T cell's journey, cell death exists as a checkpoint to limit clonal expansion and to terminate unrestrained responses. Here, we compare and contrast the T cell tolerance checkpoints and discuss their specific roles, with the aim of providing an integrated view of T cell peripheral tolerance and fate regulation.
Identifiants
pubmed: 33077935
doi: 10.1038/s41577-020-00454-2
pii: 10.1038/s41577-020-00454-2
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
257-267Subventions
Organisme : NIAID NIH HHS
ID : R01 AI148430
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR070760
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA214062
Pays : United States
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