ArticleBlood2013
Perforin deficiency impairs a critical immunoregulatory loop involving murine CD8(+) T cells and dendritic cells.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses 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
82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 132 citations in OpenAlex.
- Immunopathology of and potential therapeutics for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome: a translational perspective.Experimental & molecular medicine · 2024Pooled it
- Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: Recommendations from the North American Consortium for Histiocytosis (NACHO).Pediatric blood & cancer · 2019Guideline
- T-Cell Memory Affects Lung Responses to Cecal Ligation and Puncture.Shock (Augusta, Ga.) · 2026Article
- Exploratory study of PD-1 inhibitors with or without ruxolitinib for the treatment of adult EBV-associated hemophagocytic lymphohistiocytosis: a real-world data-based preliminary investigation.Clinical and experimental medicine · 2026Article
- EomesoderminImmunity · 2025Article
- Hemophagocytic lymphohistiocytosis caused by dual mutations in UNC13D and STX11 induced by HHV-7: a case report and review of the literature.Annals of hematology · 2025Review
- Histiocyte Society blueprint for hemophagocytic lymphohistiocytosis research: deciphering underlying disease mechanisms to optimize diagnosis and therapy.Haematologica · 2025Review
- Cytotoxic T Cells: Kill, Memorize, and Mask to Maintain Immune Homeostasis.International journal of molecular sciences · 2025Review
- Article
- Interleukin-17A signaling promotes CD8+ T cell cytotoxicity against West Nile virus infection through enhancing PI3K-mTOR-mediated metabolism.PLoS pathogens · 2025Article
- T-ing up the storm: pathogenic cycling lymphocytes in the biology of macrophage activation syndrome.Pediatric rheumatology online journal · 2025Review
- The Microbiome Modifies Manifestations of Hemophagocytic Lymphohistiocytosis in Perforin-Deficient Mice.European journal of immunology · 2025Article
- Immunological mechanisms in steatotic liver diseases: An overview and clinical perspectives.Clinical and molecular hepatology · 2024Review
- Germline variants in acquired aplastic anemia: current knowledge and future perspectives.Haematologica · 2024Review
- Patients and mice with deficiency in the SNARE protein SYNTAXIN-11 have a secondary B cell defect.The Journal of experimental medicine · 2024Article
- Murine Models of Secondary Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- Functional role of UNC13D in immune diseases and its therapeutic applications.Frontiers in immunology · 2024Review
- Salvage Therapy and Allogeneic Hematopoietic Cell Transplantation for the Severe Cytokine Storm Syndrome of Hemophagocytic Lymphohistiocytosis.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
22 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
2 authors at 1 institution in 1 country.
Funding
Abstract
Humans and mice with impaired perforin-dependent cytotoxic function may develop excessive T-cell activation and the fatal disorder hemophagocytic lymphohistiocytosis (HLH) after infection. Though cytotoxic lymphocytes can kill antigen-presenting cells, the physiological mechanism of perforin-mediated immune regulation has never been demonstrated in a disease-relevant context. We used a murine model of HLH to examine how perforin controls immune activation, and we have defined a feedback loop that is critical for immune homeostasis. This endogenous feedback loop involves perforin-dependent elimination of rare, antigen-presenting dendritic cells (DCs) by CD8(+) T cells and has a dominant influence on the magnitude of T-cell activation after viral infection. Antigen presentation by a minor fraction of DCs persisted in T-cell- or perforin-deficient animals and continued to drive T-cell activation well beyond initial priming in the latter animals. Depletion of DCs or transfer of perforin-sufficient T cells dampened endogenous DC antigen presentation and T-cell activation, demonstrating a reciprocal relationship between perforin in CD8(+) T cells and DC function. Thus, selective cytotoxic "pruning" of DC populations by CD8(+) T cells limits T-cell activation and protects against the development of HLH and potentially other immunopathological conditions.
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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.