The DOI matches its Crossref record; 221 of the 221 references it cites were found in a registry or an index.
Rethinking peripheral T cell tolerance: checkpoints across a T cell’s journey
Abstract
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. A number of T cell-intrinsic peripheral tolerance mechanisms (quiescence, ignorance, anergy, exhaustion, senescence and cell death) restrain autoimmunity and overactive immune responses. Here, the authors provide an integrated perspective of peripheral T cell tolerance by comparing the molecular mechanisms that govern these checkpoints and discussing their role in T cell tolerance and fate regulation.
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Cites
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Chu, Y., Dai, E., Li, Y., Han, G., Pei, G., Ingram, D. R., Thakkar, K., Qin, J.-J., Dang, M., Le, X., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02371-y · Cited by 478
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Metadata
- Authors
- ElTanbouly, M. A., & Noelle, R. J.
- Venue
- Nature Reviews Immunology
- Published
- 2020-10-19
- Volume
- 21
- Issue
- 4
- Pages
- 257-267
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- OpenAlex
- W3093086753
- Cited by
- 265
- References
- 221
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- closed
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