Activation-induced cell death in human T cells is a suicidal process regulated by cell density but superantigen induces T cell fratricide

2002 ◽  
Vol 219 (2) ◽  
pp. 98-107 ◽  
Author(s):  
Patricia Gorak-Stolinska ◽  
David M. Kemeny ◽  
Alistair Noble
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Cell Density ◽  
Activation Induced Cell Death ◽  
Human T Cells

scholarly journals T Cell Receptor-induced Activation and Apoptosis In Cycling Human T Cells Occur throughout the Cell Cycle

1999 ◽  
Vol 10 (12) ◽  
pp. 4441-4450 ◽  
Author(s):  
Michael Karas ◽  
Tal Z. Zaks ◽  
Liu JL ◽  
Derek LeRoith
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
T Cell Receptor ◽  
Fas Ligand ◽  
Cell Receptor ◽  
Receptor Activation ◽  
Activation Induced Cell Death ◽  
Human T Cells

Previous studies have found conflicting associations between susceptibility to activation-induced cell death and the cell cycle in T cells. However, most of the studies used potentially toxic pharmacological agents for cell cycle synchronization. A panel of human melanoma tumor-reactive T cell lines, a CD8+ HER-2/neu-reactive T cell clone, and the leukemic T cell line Jurkat were separated by centrifugal elutriation. Fractions enriched for the G0–G1, S, and G2–M phases of the cell cycle were assayed for T cell receptor-mediated activation as measured by intracellular Ca2+flux, cytolytic recognition of tumor targets, and induction of Fas ligand mRNA. Susceptibility to apoptosis induced by recombinant Fas ligand and activation-induced cell death were also studied. None of the parameters studied was specific to a certain phase of the cell cycle, leading us to conclude that in nontransformed human T cells, both activation and apoptosis through T cell receptor activation can occur in all phases of the cell cycle.

scholarly journals Fas ligand mediates activation-induced cell death in human T lymphocytes.

1995 ◽  
Vol 181 (1) ◽  
pp. 71-77 ◽  
Author(s):  
M R Alderson ◽  
T W Tough ◽  
T Davis-Smith ◽  
S Braddy ◽  
B Falk ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Fas Ligand ◽  
Significant Proportion ◽  
Cell Receptor ◽  
Target Cells ◽  
Activated T Cells ◽  
Activation Induced Cell Death ◽  
Fas L

A significant proportion of previously activated human T cells undergo apoptosis when triggered through the CD3/T cell receptor complex, a process termed activation-induced cell death (AICD). Ligation of Fas on activated T cells by either Fas antibodies or recombinant human Fas-ligand (Fas-L) also results in cytolysis. We demonstrate that these two pathways of apoptosis are causally related. Stimulation of previously activated T cells resulted in the expression of Fas-L mRNA and lysis of Fas-positive target cells. Fas-L antagonists inhibited AICD of T cell clones and staphylococcus enterotoxin B (SEB)-specific T cell lines. The data indicate AICD in previously stimulated T cells is mediated by Fas/Fas-L interactions.

scholarly journals The Caspase 8 Inhibitor c-FLIPL Modulates T-Cell Receptor-Induced Proliferation but Not Activation-Induced Cell Death of Lymphocytes

2002 ◽  
Vol 22 (15) ◽  
pp. 5419-5433 ◽  
Author(s):  
Susanne M. A. Lens ◽  
Takao Kataoka ◽  
Karen A. Fortner ◽  
Antoine Tinel ◽  
Isabel Ferrero ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
T Cell Receptor ◽  
Death Receptor ◽  
Cell Receptor ◽  
Caspase 8 ◽  
Activation Induced Cell Death

ABSTRACT The caspase 8 inhibitor c-FLIPL can act in vitro as a molecular switch between cell death and growth signals transmitted by the death receptor Fas (CD95). To elucidate its function in vivo, transgenic mice were generated that overexpress c-FLIPL in the T-cell compartment (c-FLIPL Tg mice). As anticipated, FasL-induced apoptosis was inhibited in T cells from the c-FLIPL Tg mice. In contrast, activation-induced cell death of T cells in c-FLIPL Tg mice was unaffected, suggesting that this deletion process can proceed in the absence of active caspase 8. Accordingly, c-FLIPL Tg mice differed from Fas-deficient mice by showing no accumulation of B220+ CD4− CD8− T cells. However, stimulation of T lymphocytes with suboptimal doses of anti-CD3 or antigen revealed increased proliferative responses in T cells from c-FLIPL Tg mice. Thus, a major role of c-FLIPL in vivo is the modulation of T-cell proliferation by decreasing the T-cell receptor signaling threshold.

Glucocorticoids inhibit activation-induced cell death (AICD) via direct DNA-dependent repression of the CD95 ligand gene by a glucocorticoid receptor dimer

Blood ◽  
2005 ◽  
Vol 106 (2) ◽  
pp. 617-625 ◽  
Author(s):  
Sven Baumann ◽  
Anja Dostert ◽  
Natalia Novac ◽  
Anton Bauer ◽  
Wolfgang Schmid ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Glucocorticoid Receptor ◽  
Fas Ligand ◽  
Regulatory Elements ◽  
Activated T Cells ◽  
Activation Induced Cell Death

Abstract Glucocorticoids (GCs) play an important role in the regulation of peripheral T-cell survival. Their molecular mechanism of action and the question of whether they have the ability to inhibit apoptosis in vivo, however, are not fully elucidated. Signal transduction through the glucocorticoid receptor (GR) is complex and involves different pathways. Therefore, we used mice with T-cell-specific inactivation of the GR as well as mice with a function-selective mutation in the GR to determine the signaling mechanism. Evidence is presented for a functional role of direct binding of the GR to 2 negative glucocorticoid regulatory elements (nGREs) in the CD95 (APO-1/Fas) ligand (L) promoter. Binding of GRs to these nGREs reduces activation-induced CD95L expression in T cells. These in vitro results are fully supported by data obtained in vivo. Administration of GCs to mice leads to inhibition of activation-induced cell death (AICD). Thus, GC-mediated inhibition of CD95L expression of activated T cells might contribute to the anti-inflammatory function of steroid drugs. (Blood. 2005;106:617-625)

scholarly journals Regulation of FAS Ligand Expression during Activation-Induced Cell Death in T Cells by p38 Mitogen-Activated Protein Kinase and C-Jun Nh2-Terminal Kinase

2000 ◽  
Vol 191 (6) ◽  
pp. 1017-1030 ◽  
Author(s):  
Jian Zhang ◽  
Jian-Xin Gao ◽  
Kostantin Salojin ◽  
Qing Shao ◽  
Marsha Grattan ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Protein Kinase ◽  
P38 Mapk ◽  
Fas Ligand ◽  
Mitogen Activated Protein Kinase ◽  
Fasl Expression ◽  
Activation Induced Cell Death ◽  
Mitogen Activated Protein

Activation-induced cell death (AICD) is a mechanism of peripheral T cell tolerance that depends upon an interaction between Fas and Fas ligand (FasL). Although c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) may be involved in apoptosis in various cell types, the mode of regulation of FasL expression during AICD in T cells by these two MAPKs is incompletely understood. To investigate the regulatory roles of these two MAPKs, we analyzed the kinetics of TCR-induced p38 MAPK and JNK activity and their regulation of FasL expression and AICD. We report that both JNK and p38 MAPK regulate AICD in T cells. Our data suggest a novel model of T cell AICD in which p38 MAPK acts early to initiate FasL expression and the Fas-mediated activation of caspases. Subsequently, caspases stimulate JNK to further upregulate FasL expression. Thus, p38 MAPK and downstream JNK converge to regulate FasL expression at different times after T cell receptor stimulation to elicit maximum AICD.

scholarly journals Inhibition of Superoxide Generation upon T-Cell Receptor Engagement Rescues Mart-127-35–Reactive T Cells from Activation-Induced Cell Death

2009 ◽  
Vol 69 (15) ◽  
pp. 6282-6289 ◽  
Author(s):  
Håkan Norell ◽  
Telma Martins da Palma ◽  
Aaron Lesher ◽  
Navtej Kaur ◽  
Meenal Mehrotra ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Superoxide Generation ◽  
Activation Induced Cell Death
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