ArticleBlood2011
Perforin is a critical physiologic regulator of T-cell activation.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: Recommendations from the North American Consortium for Histiocytosis (NACHO).Pediatric blood & cancer · 2019Guideline
- HLHRUXO: a prospective trial of a ruxolitinib-containing regimen for children with hemophagocytic lymphohistiocytosis.Blood advances · 2026Trial
- Clinical-Pathological Conference Series from the Medical University of Graz : Case No 186: A 33-year-old plumber with fever and acute liver injury.Wiener klinische Wochenschrift · 2026Article
- Pharmacological inhibition of perforin dampens CD8Diabetologia · 2026Article
- Immune checkpoint inhibitor-induced myocarditis is dependent on CD8 T cell-derived TNF and TNFR2 signaling.The Journal of experimental medicine · 2026Article
- Cytotoxic T Cells: Kill, Memorize, and Mask to Maintain Immune Homeostasis.International journal of molecular sciences · 2025Review
- Article
- Editorial: Community series in the regulation of the host immune activation in respiratory virus infections, volume II.Frontiers in immunology · 2025Article
- Diagnostic Challenges in Hemophagocytic Lymphohistiocytosis, a Rare, Potentially Fatal Disease: Two Case Studies.Journal of clinical medicine · 2024Review
- Cytokines in Cytokine Storm Syndrome.Advances in experimental medicine and biology · 2024Review
- Genetics of Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis.Advances in experimental medicine and biology · 2024Review
- Murine Models of Familial Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- Autoinflammatory Contributors to Cytokine Storm.Advances in experimental medicine and biology · 2024Review
- Complementary HLH susceptibility factors converge on CD8 T-cell hyperactivation.Blood advances · 2023Article
- Diagnosis and Management of Adult Malignancy-Associated Hemophagocytic Lymphohistiocytosis.Cancers · 2023Review
- sCD25 as an independent adverse prognostic factor in adult patients with HLH: results of a multicenter retrospective study.Blood advances · 2023Article
- Insights into the cellular pathophysiology of familial hemophagocytic lymphohistiocytosis.Frontiers in immunology · 2023Review
- Cytokine Storm-Definition, Causes, and Implications.International journal of molecular sciences · 2022Review
- Immune cell-mediated features of non-alcoholic steatohepatitis.Nature reviews. Immunology · 2022Review
- Interferon-gamma and perforin-positive T cells in acquired aplastic anemia: implication in therapeutic response.Clinical and experimental immunology · 2022Article
20 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
5 authors at 1 institution in 1 country.
Funding
Abstract
Individuals with impaired perforin-dependent cytotoxic function (Ctx(-)) develop a fatal inflammatory disorder called hemophagocytic lymphohistiocytosis (HLH). It has been hypothesized that immune hyperactivation during HLH is caused by heightened infection, defective apoptosis/responsiveness of Ctx(-) lymphocytes, or enhanced antigen presentation. Whereas clinical and experimental data suggest that increased T-cell activation drives HLH, potential abnormalities of T-cell activation have not been well characterized in Ctx(-) hosts. To define such abnormalities and to test these hypotheses, we assessed in vivo T-cell activation kinetics and viral loads after lymphocytic choriomeningitis virus (LCMV) infection of Ctx(-) mice. We found that increased T-cell activation occurred early during infection of Ctx(-) mice, while they had viral burdens that were identical to those of WT animals, demonstrating that T-cell hyperactivation was independent of viral load. Furthermore, cell transfer and signaling studies indicated that increased antigenic stimulation, not a cell-intrinsic defect of responsiveness, underlay heightened T-cell activation in vivo. Finally, direct measurement of viral antigen presentation demonstrated an increase in Ctx(-) mice that was proportional to abnormal T-cell activation. We conclude that perforin-dependent cytotoxicity has an immunoregulatory role that is distinguishable from its pathogen clearance function and limits T-cell activation in the physiologic context by suppressing antigen presentation.
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What OpenQuestion holds
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.