ArticleThe Journal of clinical investigation2009
Restimulation-induced apoptosis of T cells is impaired in patients with X-linked lymphoproliferative disease caused by SAP deficiency.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.
- Guideline
- NDRG3 is essential for sustaining antigen-driven T cell responses by protecting against restimulation-induced cell death.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Polyclonal evolution of lymphoproliferative disorders in XLP1.Journal of human immunity · 2026Article
- PD-1 protects expanding human T cells from premature restimulation-induced cell death by modulating TCR and CD28 signaling.Cell death & disease · 2026Article
- Article
- SLAMF receptors: key regulators of tumor progression and emerging targets for cancer immunotherapy.Molecular cancer · 2025Review
- Imaging of biphasic signalosomes constructed by checkpoint receptor 2B4 in conventional and chimeric antigen receptor-T cells.iScience · 2025Article
- X-linked lymphoproliferative disease type 1: a clinical and genetic update.Frontiers in immunology · 2025Review
- Lentiviral vectors for precise expression to treat X-linked lymphoproliferative disease.Molecular therapy. Methods & clinical development · 2024Article
- Article
- A20 intrinsically influences human effector T-cell survival and function by regulating both NF-κB and JNK signaling.European journal of immunology · 2024Article
- SLAM/SAP signaling regulates discrete γδ T cell developmental checkpoints and shapes the innate-like γδ TCR repertoire.bioRxiv : the preprint server for biology · 2024Article
- Apoptosis, a Metabolic "Head-to-Head" between Tumor and T Cells: Implications for Immunotherapy.Cells · 2024Review
- Infectious Triggers of Cytokine Storm Syndromes: Herpes Virus Family (Non-EBV).Advances in experimental medicine and biology · 2024Review
- Salvage Therapy and Allogeneic Hematopoietic Cell Transplantation for the Severe Cytokine Storm Syndrome of Hemophagocytic Lymphohistiocytosis.Advances in experimental medicine and biology · 2024Review
- Complementary HLH susceptibility factors converge on CD8 T-cell hyperactivation.Blood advances · 2023Article
- Molecular and temporal control of restimulation-induced cell death (RICD) in T lymphocytes.Frontiers in cell death · 2023Article
- The hyperinflammatory spectrum: from defects in cytotoxicity to cytokine control.Frontiers in immunology · 2023Review
- Regulation of activated T cell survival in rheumatic autoimmune diseases.Nature reviews. Rheumatology · 2022Review
- Immune Checkpoint Receptors Signaling in T Cells.International journal of molecular sciences · 2022Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
X-linked lymphoproliferative disease (XLP) is a rare congenital immunodeficiency that leads to an extreme, usually fatal increase in the number of lymphocytes upon infection with EBV. It is most commonly defined molecularly by loss of expression of SLAM-associated protein (SAP). Despite this, there is little understanding of how SAP deficiency causes lymphocytosis following EBV infection. Here we show that T cells from individuals with XLP are specifically resistant to apoptosis mediated by TCR restimulation, a process that normally constrains T cell expansion during immune responses. Expression of SAP and the SLAM family receptor NK, T, and B cell antigen (NTB-A) were required for TCR-induced upregulation of key pro-apoptotic molecules and subsequent apoptosis. Further, SAP/NTB-A signaling augmented the strength of the proximal TCR signal to achieve the threshold required for restimulation-induced cell death (RICD). Strikingly, TCR ligation in activated T cells triggered increased recruitment of SAP to NTB-A, dissociation of the phosphatase SHP-1, and colocalization of NTB-A with CD3 aggregates. In contrast, NTB-A and SHP-1 contributed to RICD resistance in XLP T cells. Our results reveal what we believe to be novel roles for NTB-A and SAP in regulating T cell homeostasis through apoptosis and provide mechanistic insight into the pathogenesis of lymphoproliferative disease in XLP.
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Registered trials
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.