ArticleThe Journal of experimental medicine2009
CD95 co-stimulation blocks activation of naive T cells by inhibiting T cell receptor signaling.
Article in The Journal of experimental medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 47 citations in OpenAlex.
- Circulating cell populations as response predictors and targets to improve immunotherapy in metastatic lung cancer.iScience · 2026Article
- A PI3Kδ-Foxo1-FasL signaling amplification loop rewires CD4+ T cell signaling and differentiation.The Journal of experimental medicine · 2026Article
- Ceramide signaling in immunity: a molecular perspective.Lipids in health and disease · 2025Review
- Immune mechanisms and predictive biomarkers related to neoadjuvant immunotherapy response in stage III melanoma.Heliyon · 2024Article
- Correlation of High-Grade Osteosarcoma Response to Chemotherapy with Enhanced Tissue Immunological Response: Analysis of CD95R, IFN-γ, Catalase, Hsp70, and VEGF.Virchows Archiv : an international journal of pathology · 2024Article
- Characterizing the regulatory Fas (CD95) epitope critical for agonist antibody targeting and CAR-T bystander function in ovarian cancer.Cell death and differentiation · 2023Article
- A Story of Kinases and Adaptors: The Role of Lck, ZAP-70 and LAT in Switch Panel Governing T-Cell Development and Activation.Biology · 2023Review
- A Stretch of Negatively Charged Amino Acids of Linker for Activation of T-Cell Adaptor Has a Dual Role in T-Cell Antigen Receptor Intracellular Signaling.Frontiers in immunology · 2018Article
- ArtinM Mediates Murine T Cell Activation and Induces Cell Death in Jurkat Human Leukemic T Cells.International journal of molecular sciences · 2017Article
- On How Fas Apoptosis-Independent Pathways Drive T Cell Hyperproliferation and Lymphadenopathy inFrontiers in immunology · 2017Article
- The mucin MUC1 modulates the tumor immunological microenvironment through engagement of the lectin Siglec-9.Nature immunology · 2016Article
- Life in the Fas lane: differential outcomes of Fas signaling.Cellular and molecular life sciences : CMLS · 2013Review
- FcRγ controls the fas-dependent regulatory function of lymphoproliferative double negative T cells.PloS one · 2013Article
- CD95-mediated cell signaling in cancer: mutations and post-translational modulations.Cellular and molecular life sciences : CMLS · 2012Review
- Pathogen-induced proapoptotic phenotype and high CD95 (Fas) expression accompany a suboptimal CD8+ T-cell response: reversal by adenoviral vaccine.PLoS pathogens · 2012Article
- In vitro-established alloantigen-specific CD8+ CTLs mediate graft-versus-tumor activity in the absence of graft-versus-host disease.Leukemia · 2011Article
- Pro- and anti-apoptotic CD95 signaling in T cells.Cell communication and signaling : CCS · 2011Article
- Modulation of CD4+ T-cell activation by CD95 co-stimulation.Cell death and differentiation · 2011Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD95 is a multifunctional receptor that induces cell death or proliferation depending on the signal, cell type, and cellular context. Here, we describe a thus far unknown function of CD95 as a silencer of T cell activation. Naive human T cells triggered by antigen-presenting cells expressing a membrane-bound form of CD95 ligand (CD95L) or stimulated by anti-CD3 and -CD28 antibodies in the presence of recombinant CD95L had reduced activation and proliferation, whereas preactivated, CD95-sensitive T cells underwent apoptosis. Triggering of CD95 during T cell priming interfered with proximal T cell receptor signaling by inhibiting the recruitment of zeta-chain-associated protein of 70 kD, phospholipase-gamma, and protein kinase C- into lipid rafts, thereby preventing their mutual tyrosine protein phosphorylation. Subsequently, Ca(2+) mobilization and nuclear translocation of transcription factors NFAT, AP1, and NF-kappaB were strongly reduced, leading to impaired cytokine secretion. CD95-mediated inhibition of proliferation in naive T cells could not be reverted by the addition of exogenous interleukin-2 and T cells primed by CD95 co-stimulation remained partially unresponsive upon secondary T cell stimulation. HIV infection induced CD95L expression in primary human antigen-presenting cells, and thereby suppressed T cell activation, suggesting that CD95/CD95L-mediated silencing of T cell activation represents a novel mechanism of immune evasion.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.