scholarly journals Immature thymocytes become sensitive to calcium-mediated apoptosis with the onset of CD8, CD4, and the T cell receptor expression: a role for bcl-2?

1993 ◽  
Vol 178 (5) ◽  
pp. 1745-1751 ◽  
Author(s):  
S Andjelić ◽  
N Jain ◽  
J Nikolić-Zugić
Keyword(s):  
Cell Death ◽  
T Cell ◽  
T Cell Receptor ◽  
Apoptotic Cell ◽  
Calcium Ionophore ◽  
Cell Receptor ◽  
Receptor Expression ◽  
Clonal Deletion ◽  
Induced Apoptosis ◽  
Precursor Activity

During intrathymic negative selection by clonal deletion, crosslinking of the T cell receptor (TCR) induces cell death by delivering an apoptotic signal(s) to the nucleus along a calcium-dependent pathway. We investigated the reactivity of early precursor-containing thymocytes to Ca(2+)-induced signals, and discovered a breakpoint in their sensitivity to calcium-mediated cell death (CMCD). CD25+CD8-4- TCR- (triple negative [TN]) thymocytes stimulated with a calcium ionophore maintain their viability and precursor activity. By contrast, their immediate progeny, CD25-CD8lo4loTCR alpha beta lo (triple low [TL]) cells react to calcium elevation by abrogation of precursor activity and apoptotic cell death. This developmental difference is specific for CMCD, since both CD25+TN and CD25-TL cells are susceptible to steroid-induced apoptosis. The presence of bcl-2 mRNA correlates directly to the resistance to CMCD-CD25+ TN cells express it and CD25-TL cells do not. These experiments show that thymocytes become sensitive to Ca(2+)-induced apoptosis as soon as they begin to express molecules that mediate thymic selection, and suggest that a concomitant downregulation of bcl-2 may mediate this phenomenon.

scholarly journals 9-cis retinoic acid inhibition of activation-induced apoptosis is mediated via regulation of fas ligand and requires retinoic acid receptor and retinoid X receptor activation.

1995 ◽  
Vol 15 (10) ◽  
pp. 5576-5585 ◽  
Author(s):  
R P Bissonnette ◽  
T Brunner ◽  
S B Lazarchik ◽  
N J Yoo ◽  
M F Boehm ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
T Cell ◽  
T Cell Receptor ◽  
Target Genes ◽  
Fas Ligand ◽  
Apoptotic Cell ◽  
Cell Receptor ◽  
Receptor Activation ◽  
Retinoid Receptor ◽  
Induced Apoptosis

T-cell hybridomas, thymocytes, and T cells can be induced to undergo apoptotic cell death by activation through the T-cell receptor. This process requires macromolecular synthesis and thus gene expression, and it has been shown to be influenced by factors regulating transcription. Recently, activation, T-cell hybridomas rapidly express the Fas/CD95 receptor and its ligand, Fas ligand (FasL), which interact to transduce the death signal in the activated cell. Retinoids, the active metabolites of vitamin A, modulate expression of specific target genes by binding to two classes of intracellular receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs). They are potent modulators of apoptosis in a number of experimental models, and they have been shown to inhibit activation-induced apoptosis in T-cell hybridomas and thymocytes. Particularly effective is the prototypic pan-agonist 9-cis retinoic acid (9-cis RA), which has high affinity for both RARs and RXRs. We report here that 9-cis RA inhibits T-cell receptor-mediated apoptosis in T-cell hybridomas by blocking the expression of Fas ligand following activation. This inhibition appears to be at the level of FasL mRNA, with the subsequent failure to express cell surface FasL. RAR-selective (TTNPB) or RXR-selective (LG100268) ligands alone were considerably less potent than RAR-RXR pan-agonists. However, the addition of both RAR- and RXR-selective ligands was as effective as the addition of 9-cis RA alone. The demonstrates that the inhibitory effect requires the ligand-mediated activation of both retinoid receptor signaling pathways.

Distinct Regulation of T-Cell Death by CD28 Depending on Both Its Aggregation and T-Cell Receptor Triggering: A Role for Fas-FasL

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1350-1363 ◽  
Author(s):  
Y. Collette ◽  
A. Benziane ◽  
D. Razanajaona ◽  
D. Olive
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Clone ◽  
Cell Receptor ◽  
Fasl Expression ◽  
T Cell Clone ◽  
Induced Apoptosis

CD28 is a major coreceptor that regulates cell proliferation, anergy, and viability of T cells. The negative selection by T-cell receptor (TCR)-induced cell death of immature thymocytes as well as of activated human antigen-specific T-cell clone, requires a costimulatory signal that can be provided by CD28. Conversely, CD28-mediated signals increase expression of Bcl-XL, a survival gene, and promote survival of naive T cells cultured in the absence of antigen or costimulation. Because CD28 appears to both protect from, or induce T-cell death, one important question is to define the activation and cellular parameters that dictate the differential role of CD28 in T-cell apoptosis. Here, we compared different CD28 ligands for their ability to regulate TCR-induced cell death of a murine T-cell hybridoma. In these cells, TCR triggering induced expression of Fas and FasL, and cell death was prevented by anti-Fas blocking monoclonal antibody (MoAb). When provided as a costimulus, both CD28 MoAb and the B7.1 and B7.2 counter receptors downregulated, yet did not completely abolish T-cell receptor–induced apoptosis. This CD28 cosignal resulted in both upregulation of Bcl-XL and prevention of FasL expression. In marked contrast, when given as a single signal, CD28 MoAb or B7.1 and B7.2 induced FasL expression and resulted in T-cell death by apoptosis, which was dependent on the level of CD28 ligation. Furthermore, triggering of CD28 upregulated FasL and induced a marked T-cell death of previously activated normal peripheral T cells. Our results identify Fas and FasL as crucial targets of CD28 in T-cell death regulation and show that within the same cell population, depending on its engagement as a single signal or as a costimulus together with the TCR, CD28 can either induce a dose-dependent death signal or protect from cell death, respectively. These data provide important insights into the role of CD28 in T-cell homeostasis and its possible implication in neoplastic disorders. © 1998 by The American Society of Hematology.

Distinct Regulation of T-Cell Death by CD28 Depending on Both Its Aggregation and T-Cell Receptor Triggering: A Role for Fas-FasL

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1350-1363 ◽  
Author(s):  
Y. Collette ◽  
A. Benziane ◽  
D. Razanajaona ◽  
D. Olive
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Clone ◽  
Cell Receptor ◽  
Fasl Expression ◽  
T Cell Clone ◽  
Induced Apoptosis

Abstract CD28 is a major coreceptor that regulates cell proliferation, anergy, and viability of T cells. The negative selection by T-cell receptor (TCR)-induced cell death of immature thymocytes as well as of activated human antigen-specific T-cell clone, requires a costimulatory signal that can be provided by CD28. Conversely, CD28-mediated signals increase expression of Bcl-XL, a survival gene, and promote survival of naive T cells cultured in the absence of antigen or costimulation. Because CD28 appears to both protect from, or induce T-cell death, one important question is to define the activation and cellular parameters that dictate the differential role of CD28 in T-cell apoptosis. Here, we compared different CD28 ligands for their ability to regulate TCR-induced cell death of a murine T-cell hybridoma. In these cells, TCR triggering induced expression of Fas and FasL, and cell death was prevented by anti-Fas blocking monoclonal antibody (MoAb). When provided as a costimulus, both CD28 MoAb and the B7.1 and B7.2 counter receptors downregulated, yet did not completely abolish T-cell receptor–induced apoptosis. This CD28 cosignal resulted in both upregulation of Bcl-XL and prevention of FasL expression. In marked contrast, when given as a single signal, CD28 MoAb or B7.1 and B7.2 induced FasL expression and resulted in T-cell death by apoptosis, which was dependent on the level of CD28 ligation. Furthermore, triggering of CD28 upregulated FasL and induced a marked T-cell death of previously activated normal peripheral T cells. Our results identify Fas and FasL as crucial targets of CD28 in T-cell death regulation and show that within the same cell population, depending on its engagement as a single signal or as a costimulus together with the TCR, CD28 can either induce a dose-dependent death signal or protect from cell death, respectively. These data provide important insights into the role of CD28 in T-cell homeostasis and its possible implication in neoplastic disorders. © 1998 by The American Society of Hematology.

Analysis of Function, Specificity and T Cell Receptor Expression of Cloned Mucosal T Cell Lines in Crohn's Disease

1996 ◽  
Vol 9 (2) ◽  
pp. 193-204 ◽  
Author(s):  
Thomas P. Prindiville ◽  
Mary C. Cantrell ◽  
Takayuki Matsumoto ◽  
William R. Brown ◽  
Aftab A. Ansari ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
T Cell ◽  
Crohn's Disease ◽  
T Cell Receptor ◽  
Cell Lines ◽  
Cell Receptor ◽  
Receptor Expression ◽  
T Cell Lines ◽  
Analysis Of Function

scholarly journals T cell receptor-dependent cell death of T cell hybridomas mediated by the CD30 cytoplasmic domain in association with tumor necrosis factor receptor-associated factors.

1996 ◽  
Vol 183 (2) ◽  
pp. 669-674 ◽  
Author(s):  
S Y Lee ◽  
C G Park ◽  
Y Choi
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
T Cell Receptor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Cell Receptor ◽  
Cytoplasmic Domain ◽  
Activated T Cells ◽  
Necrosis Factor

CD30 is a member of the tumor necrosis factor superfamily and a surface marker for Hodgkin's disease. Normal activated T cells and several virally transformed T or B cell lines also show CD30 expression. The interaction of CD30 with its ligand induces cell death or proliferation, depending on the cell type. In this report we characterize the signals mediated by the intracellular domain of CD30 and show that, in combination with signal(s) transduced by the T cell receptor, the multimerization of CD30 cytoplasmic domain induces Fas(CD95)-independent cell death in T cell hybridomas. Deletion analysis shows that the COOH-terminal 66 amino acids of CD30 are required to induce cell death. Using the yeast two-hybrid system, we have identified that the same region of CD30 interacts with tumor necrosis factor receptor-associated factor (TRAF)1 and TRAF2. These results indicate that TRAF1 and/or TRAF2 play an important role in cell death in addition to their previously identified roles in cell proliferation.

Cell Biology of T Cell Receptor Expression and Regulation

2018 ◽  
Vol 36 (1) ◽  
pp. 103-125 ◽  
Author(s):  
Andrés Alcover ◽  
Balbino Alarcón ◽  
Vincenzo Di Bartolo
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Biology ◽  
Cell Receptor ◽  
Receptor Expression
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