ArticleJournal of virology1999
A role for perforin in downregulating T-cell responses during chronic viral infection.
Article in Journal of virology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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
65 citing papers in PubMed, 222 citations in OpenAlex.
- Cytotoxic T Cells: Kill, Memorize, and Mask to Maintain Immune Homeostasis.International journal of molecular sciences · 2025Review
- CD8Advances in experimental medicine and biology · 2024Review
- Insights into the cellular pathophysiology of familial hemophagocytic lymphohistiocytosis.Frontiers in immunology · 2023Review
- 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
- Sphingosine kinase 2 restricts T cell immunopathology but permits viral persistence.The Journal of clinical investigation · 2020Article
- Perforin-deficient CAR T cells recapitulate late-onset inflammatory toxicities observed in patients.The Journal of clinical investigation · 2020Article
- Disruption of IL-33 Signaling Limits Early CD8+ T Cell Effector Function Leading to Exhaustion in Murine Hemophagocytic Lymphohistiocytosis.Frontiers in immunology · 2018Article
- Telomere Dynamics in Immune Senescence and Exhaustion Triggered by Chronic Viral Infection.Viruses · 2017Review
- Dendritic cells, macrophages, NK and CD8Virology journal · 2017Article
- ST2 contributes to T-cell hyperactivation and fatal hemophagocytic lymphohistiocytosis in mice.Blood · 2016Article
- Intrinsic Contribution of Perforin to NK-Cell Homeostasis during Mouse Cytomegalovirus Infection.Frontiers in immunology · 2016Article
- CD8 T cells and Mycobacterium tuberculosis infection.Seminars in immunopathology · 2015Review
- Chronic HCV infection affects the NK cell phenotype in the blood more than in the liver.PloS one · 2014Article
- Large T Antigen-Specific Cytotoxic T Cells Protect Against Dendritic Cell Tumors through Perforin-Mediated Mechanisms Independent of CD4 T Cell Help.Frontiers in immunology · 2014Article
- Article
- Inefficient boosting of antitumor CD8(+) T cells by dendritic-cell vaccines is rescued by restricting T-cell cytotoxic functions.Oncoimmunology · 2012Article
- Contribution of NK cells to the innate phase of host protection against an intracellular bacterium targeting systemic endothelium.The American journal of pathology · 2012Article
- Epitope specificity of memory CD8+ T cells dictates vaccination-induced mortality in LCMV-infected perforin-deficient mice.European journal of immunology · 2012Article
- Presentation of hemophagocytic lymphohistiocytosis due to a novel MUNC 13-4 mutation masked by partial therapeutic immunosuppression.Pediatric rheumatology online journal · 2012Article
5 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
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Cytotoxic T cells secrete perforin to kill virus-infected cells. In this study we show that perforin also plays a role in immune regulation. Perforin-deficient (perf -/-) mice chronically infected with lymphocytic choriomeningitis virus (LCMV) contained greater numbers of antiviral T cells compared to persistently infected +/+ mice. The enhanced expansion was seen in both CD4 and CD8 T cells, but the most striking difference was in the numbers of LCMV-specific CD8 T cells present in infected perf -/- mice. Persistent LCMV infection of +/+ mice results in both deletion and anergy of antigen-specific CD8 T cells, and our results show that this peripheral "exhaustion" of activated CD8 T cells occurred less efficiently in perf -/- mice. This excessive accumulation of activated CD8 T cells resulted in immune-mediated damage in persistently infected perf -/- mice; approximately 50% of these mice died within 2 to 4 weeks, and mortality was fully reversed by in vivo depletion of CD8 T cells. This finding highlights an interesting dichotomy between the role of perforin in viral clearance and immunopathology; perforin-deficient CD8 T cells were unable to clear the LCMV infection but were capable of causing immune-mediated damage. Finally, this study shows that perforin also plays a role in regulating T-cell-mediated autoimmunity. Mice that were deficient in both perforin and Fas exhibited a striking acceleration of the spontaneous lymphoproliferative disease seen in Fas-deficient (lpr) mice. Taken together, these results show that the perforin-mediated pathway is involved in downregulating T-cell responses during chronic viral infection and autoimmunity and that perforin and Fas act independently as negative regulators of activated T cells.
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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.