» Articles » PMID: 30635093

T Cells and Regulated Cell Death: Kill or Be Killed

Overview
Publisher Elsevier
Date 2019 Jan 13
PMID 30635093
Citations 17
Authors
Affiliations
Soon will be listed here.
Abstract

Cell death plays two major complementary roles in T cell biology: mediating the removal of cells that are targeted by T cells and the removal of T cells themselves. T cells serve as major actors in the adaptive immune response and function by selectively killing cells which are infected or dysfunctional. This feature is highly involved during homeostatic maintenance, and is relied upon and modulated in the context of cancer immunotherapy. The vital recognition and elimination of both autoreactive T cells and cells which are unable to recognize threats is a highly selective and regulated process. Moreover, detection of potential threats will result in the activation and expansion of T cells, which on resolution of the immune response will need to be eliminated. The culling of these T cells can be executed via a multitude of cell death pathways which are used in context-specific manners. Failure of these processes may result in an accumulation of misdirected or dysfunctional T cells, leading to complications such as autoimmunity or cancer. This review will focus on the role of cell death regulation in the maintenance of T cell homeostasis, as well as T cell-mediated elimination of infected or dysfunctional cells, and will summarize and discuss the current knowledge of the cellular mechanisms which are implicated in these processes.

Citing Articles

Estrogen influences class-switched memory B cell frequency only in humans with two X chromosomes.

Peckham H, Radziszewska A, Sikora J, de Gruijter N, Restuadi R, Kartawinata M J Exp Med. 2025; 222(4).

PMID: 40049222 PMC: 11893172. DOI: 10.1084/jem.20241253.


Progress in immune microenvironment, immunotherapy and prognostic biomarkers in pediatric osteosarcoma.

Zhang L, Jiang H, Ma H Front Immunol. 2025; 16:1548527.

PMID: 39911380 PMC: 11794274. DOI: 10.3389/fimmu.2025.1548527.


Infiltrating T lymphocytes and tumor microenvironment within cholangiocarcinoma: immune heterogeneity, intercellular communication, immune checkpoints.

Dai Y, Dong C, Wang Z, Zhou Y, Wang Y, Hao Y Front Immunol. 2025; 15():1482291.

PMID: 39845973 PMC: 11750830. DOI: 10.3389/fimmu.2024.1482291.


IRF2 loss is associated with reduced MHC I pathway transcripts in subsets of most human cancers and causes resistance to checkpoint immunotherapy in human and mouse melanomas.

Sari G, Dhatchinamoorthy K, Orellano-Ariza L, Ferreira L, Brehm M, Rock K J Exp Clin Cancer Res. 2024; 43(1):276.

PMID: 39354629 PMC: 11446056. DOI: 10.1186/s13046-024-03187-5.


IRF2 loss is associated with reduced MHC I pathway transcripts in subsets of most human cancers and causes resistance to checkpoint immunotherapy in human and mouse melanomas.

Sari G, Dhatchinamoorthy K, Orellano-Ariza L, Ferreira L, Brehm M, Rock K Res Sq. 2024; .

PMID: 39281881 PMC: 11398557. DOI: 10.21203/rs.3.rs-4997954/v1.


References
1.
Hivroz C, Chemin K, Tourret M, Bohineust A . Crosstalk between T lymphocytes and dendritic cells. Crit Rev Immunol. 2012; 32(2):139-55. DOI: 10.1615/critrevimmunol.v32.i2.30. View

2.
Kovalovsky D, Pezzano M, Ortiz B, SantAngelo D . A novel TCR transgenic model reveals that negative selection involves an immediate, Bim-dependent pathway and a delayed, Bim-independent pathway. PLoS One. 2010; 5(1):e8675. PMC: 2800196. DOI: 10.1371/journal.pone.0008675. View

3.
Wang H, Sun L, Su L, Rizo J, Liu L, Wang L . Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol Cell. 2014; 54(1):133-146. DOI: 10.1016/j.molcel.2014.03.003. View

4.
Sarosiek K, Fraser C, Muthalagu N, Bhola P, Chang W, McBrayer S . Developmental Regulation of Mitochondrial Apoptosis by c-Myc Governs Age- and Tissue-Specific Sensitivity to Cancer Therapeutics. Cancer Cell. 2016; 31(1):142-156. PMC: 5363285. DOI: 10.1016/j.ccell.2016.11.011. View

5.
Chun H, Zheng L, Ahmad M, Wang J, Speirs C, Siegel R . Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature. 2002; 419(6905):395-9. DOI: 10.1038/nature01063. View