Cellular and Molecular Mechanisms of CD8<sup>+</sup> T Cell Differentiation, Dysfunction and Exhaustion
T cells follow a triphasic distinct pathway of activation, proliferation and differentiation before becoming functionally and phenotypically “exhausted” in settings of chronic infection, autoimmunity and in cancer. Exhausted T cells progressively lose canonical effector functions, exhibit altered tr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/19/7357 |
| _version_ | 1797551791721676800 |
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| author | Daniel J. Verdon Matthias Mulazzani Misty R. Jenkins |
| author_facet | Daniel J. Verdon Matthias Mulazzani Misty R. Jenkins |
| author_sort | Daniel J. Verdon |
| collection | DOAJ |
| description | T cells follow a triphasic distinct pathway of activation, proliferation and differentiation before becoming functionally and phenotypically “exhausted” in settings of chronic infection, autoimmunity and in cancer. Exhausted T cells progressively lose canonical effector functions, exhibit altered transcriptional networks and epigenetic signatures and gain constitutive expression of a broad coinhibitory receptor suite. This review outlines recent advances in our understanding of exhausted T cell biology and examines cellular and molecular mechanisms by which a state of dysfunction or exhaustion is established, and mechanisms by which exhausted T cells may still contribute to pathogen or tumour control. Further, this review describes our understanding of exhausted T cell heterogeneity and outlines the mechanisms by which checkpoint blockade differentially engages exhausted T cell subsets to overcome exhaustion and recover T cell function. |
| first_indexed | 2024-03-10T15:50:05Z |
| format | Article |
| id | doaj.art-b8e8c286e097408dbddb9f0fa2ca28aa |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:50:05Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b8e8c286e097408dbddb9f0fa2ca28aa2023-11-20T16:07:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012119735710.3390/ijms21197357Cellular and Molecular Mechanisms of CD8<sup>+</sup> T Cell Differentiation, Dysfunction and ExhaustionDaniel J. Verdon0Matthias Mulazzani1Misty R. Jenkins2Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaImmunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaImmunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaT cells follow a triphasic distinct pathway of activation, proliferation and differentiation before becoming functionally and phenotypically “exhausted” in settings of chronic infection, autoimmunity and in cancer. Exhausted T cells progressively lose canonical effector functions, exhibit altered transcriptional networks and epigenetic signatures and gain constitutive expression of a broad coinhibitory receptor suite. This review outlines recent advances in our understanding of exhausted T cell biology and examines cellular and molecular mechanisms by which a state of dysfunction or exhaustion is established, and mechanisms by which exhausted T cells may still contribute to pathogen or tumour control. Further, this review describes our understanding of exhausted T cell heterogeneity and outlines the mechanisms by which checkpoint blockade differentially engages exhausted T cell subsets to overcome exhaustion and recover T cell function.https://www.mdpi.com/1422-0067/21/19/7357T cell exhaustionchronic viral infectionscancerimmunotherapyepigeneticsPD-1 |
| spellingShingle | Daniel J. Verdon Matthias Mulazzani Misty R. Jenkins Cellular and Molecular Mechanisms of CD8<sup>+</sup> T Cell Differentiation, Dysfunction and Exhaustion International Journal of Molecular Sciences T cell exhaustion chronic viral infections cancer immunotherapy epigenetics PD-1 |
| title | Cellular and Molecular Mechanisms of CD8<sup>+</sup> T Cell Differentiation, Dysfunction and Exhaustion |
| title_full | Cellular and Molecular Mechanisms of CD8<sup>+</sup> T Cell Differentiation, Dysfunction and Exhaustion |
| title_fullStr | Cellular and Molecular Mechanisms of CD8<sup>+</sup> T Cell Differentiation, Dysfunction and Exhaustion |
| title_full_unstemmed | Cellular and Molecular Mechanisms of CD8<sup>+</sup> T Cell Differentiation, Dysfunction and Exhaustion |
| title_short | Cellular and Molecular Mechanisms of CD8<sup>+</sup> T Cell Differentiation, Dysfunction and Exhaustion |
| title_sort | cellular and molecular mechanisms of cd8 sup sup t cell differentiation dysfunction and exhaustion |
| topic | T cell exhaustion chronic viral infections cancer immunotherapy epigenetics PD-1 |
| url | https://www.mdpi.com/1422-0067/21/19/7357 |
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