TCR/CD3 coupling to Fas-based cytotoxicity.

Vignaux, Françoise; Vivier, Éric; Malissen, Bernard; Depraetere, Valérie; Nagata, Shinji; Golstein, Pierre

doi:10.1084/jem.181.2.781

Cited by 185 publications

(119 citation statements)

References 24 publications

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“…CD95L may remain sequestered in the cytosol, 81 and engagement of the TCR/CD3 complex is required to trigger T-cell death. 82 We suggest that in the absence of T-cell activation, CD95L may not reach the cell membrane in sufficiently large amounts to exert its cytotoxic potential. As T cells from SIVmac251-infected macaques are more prone to apoptosis after CD95 ligation, and may be primed to produce larger amounts of CD95L following activation, the interaction of these T cells in vivo with neighbouring CD95L-producing cells (trans), and/or after TCR triggering (cis), may increase the rate of cell death (Figure 8).…”

Section: Caspase-independentmentioning

confidence: 99%

Caspase-dependent and -independent T-cell death pathways in pathogenic simian immunodeficiency virus infection: relationship to disease progression

et al. 2003

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Studies of human immunodeficiency virus (HIV) and nonhuman primate models of pathogenic and nonpathogenic simian immunodeficiency virus (SIV) infections have suggested that enhanced ex vivo CD4 T-cell death is a feature of pathogenic infection in vivo. However, the relative contributions of the extrinsic and intrinsic pathways to programmed T-cell death in SIV infection have not been studied. We report here that the spontaneous death rate of CD4 þ T cells from pathogenic SIVmac251-infected rhesus macaques ex vivo is correlated with CD4 T-cell depletion and plasma viral load in vivo. CD4 þ T cells from SIVmac251-infected macaques showed upregulation of the death ligand (CD95L) and of the proapoptotic proteins Bim and Bak, but not of Bax. Both CD4 þ and CD8 þ T cells from SIVmac251-infected macaques underwent caspase-dependent death following CD95 ligation. The spontaneous death of CD4 þ and CD8 þ T cells was not prevented by a decoy CD95 receptor or by a broad-spectrum caspase inhibitor (zVADfmk), suggesting that this form of cell death is independent of CD95/CD95L interaction and caspase activation. IL-2 and IL-15 prevented the spontaneous death of CD4 þ and CD8 þ T cells, whereas IL-10 prevented only CD8 T-cell death and IL-7 had no effect on T-cell death. Our results indicate that caspasedependent and caspase-independent pathways are involved in the death of T cells in pathogenic SIVmac251-infected primates.

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Section: Caspase-independentmentioning

confidence: 99%

Caspase-dependent and -independent T-cell death pathways in pathogenic simian immunodeficiency virus infection: relationship to disease progression

et al. 2003

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“…Normal in vivo AICD and suppressed in vitro AICD in FLIP-transgenic T cells We next examined whether in vitro AICD, known to be Fasmediated, [30][31][32][33] was affected by FLIP transgene. NLC thymocytes stimulated with anti-CD3 underwent apoptosis, yet c- c-FLIP transgene suppresses T-cell proliferation and AICD T-S Tai et al FLIP-transgenic thymocytes were resistant to AICD (Figure 2b).…”

Section: Variable Expression Of C-flip Transgenementioning

confidence: 99%

c-FLICE inhibitory protein expression inhibits T-cell activation

Lai

2003

Cell Death Differ

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Cellular FLICE-inhibitory protein (c-FLIP) inhibits death receptor-mediated apoptosis by specific interaction with FADD and procaspase-8, and may thus interfere with activation events mediated by FADD and caspase-8. Recent studies, however, suggest that c-FLIP also transmits activation signals. The role of c-FLIP on T-cell activation was examined here using several transgenic mice with variable c-FLIP expression. In all c-FLIP-transgenic mice, Fasmediated apoptosis and in vitro activation-induced T-cell death were suppressed, and T-cell proliferation and IL-2 production were inhibited. c-FLIP transgene also promoted in vivo thymocyte death. Higher c-FLIP transgene expression was correlated with a more profound suppression of T-cell activation and a prominent disturbance in mature thymocyte development. There was no evidence of increased activation and proliferation in all c-FLIP-transgenic T cells examined. Instead, suppression of T-cell activation in c-FLIP-transgenic T cells could be a combinatory effect of FADD/caspase-8-dependent signals and c-FLIP-specific activities.

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“…In contrast, only the induction phase of Fas-based cytotoxicity is calcium-dependent; the effector phase is highly calcium-independent (24). Accordingly, day-13 cells were preincubated with plate-bound immobilized anti-CD3 MAb to up-regulate Fas ligand expression (induction phase) (25). These cells were then assayed for cytolytic activity against Fas-Daudi or Fas+ Jurkat cell targets (effector phase).…”

Section: Impaired Nonrestricted Cytolytic Activity Against Daudi Cellmentioning

confidence: 99%

Impaired nonrestricted cytolytic activity in systemic lupus erythematosus

Stohl

Elliott

et al. 1997

Arthritis & Rheumatism

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Objective. To determine the cytolytic effector pathway involved in impaired generation of nonrestricted cytolytic activity in systemic lupus erythemato- sus (SLE).Methods. Peripheral blood mononuclear cells (PBMC) from normal subjects and SLE patients were stimulated in vitro with anti-CD3 monoclonal antibody (MAb) and interleukin-2 to promote the generation of nonrestricted cytolytic activity. On day 13 of culture, the PBMC were assayed for cytolytic activity against FasDaudi cells and Fas+ Jurkat cells. The effects on cytotoxicity of calcium chelation, antagonist anti-Fas MAb, tumor necrosis factor (TNF) a and P, and ATP were measured. Intracellular perforin expression was determined by intracellular staining, and perforin messenger RNA levels were determined by quantitative competitive reverse transcription-polymerase chain reaction.Results. We demonstrated the existence of a cytolytic pathway that is independent of Fas, TNFa, TNFP, and ATP, but is dependent upon extracellular calcium. Despite its calcium dependence, this pathway is associated with low-to-undetectable levels of perforin.Conclusion. Impaired generation of nonrestricted ~-cytolytic activity in SLE is likely due to decreased activity of this Fas-, TNFa-, TNFP-, ATP-independent pathway associated with very low levels of perforin.

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TCR/CD3 coupling to Fas-based cytotoxicity.

Cited by 185 publications

References 24 publications

Caspase-dependent and -independent T-cell death pathways in pathogenic simian immunodeficiency virus infection: relationship to disease progression

Caspase-dependent and -independent T-cell death pathways in pathogenic simian immunodeficiency virus infection: relationship to disease progression

c-FLICE inhibitory protein expression inhibits T-cell activation

Impaired nonrestricted cytolytic activity in systemic lupus erythematosus

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