ArticleThe Journal of clinical investigation2000
Role of perforin in controlling B-cell hyperactivity and humoral autoimmunity.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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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.
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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
36 citing papers in PubMed, 109 citations in OpenAlex.
- Vincristine-cyclophosphamide combination therapy positively affects T-cell subset distribution in systemic lupus erythematosus patients.Medical science monitor : international medical journal of experimental and clinical research · 2015Trial
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- Type I interferon and mitochondrial dysfunction are associated with dysregulated cytotoxic CD8+ T cell responses in juvenile systemic lupus erythematosus.Clinical and experimental immunology · 2025Article
- PD-1/PD-L1 governed cross-talk of exhausted CD8RMD open · 2024Article
- Low perforin expression in CD8+ T lymphocytes during the acute phase of severe SARS-CoV-2 infection predicts long COVID.Frontiers in immunology · 2022Article
- Association of Viral Infection With the Development and Pathogenesis of Systemic Lupus Erythematosus.Frontiers in medicine · 2022Review
- Both perforin and FasL are required for optimal CD8 T cell control of autoreactive B cells and autoantibody production in parent-into-F1 lupus mice.Clinical immunology (Orlando, Fla.) · 2018Article
- The Role of Animal Models in the Study of Hematopoietic Stem Cell Transplantation and GvHD: A Historical Overview.Frontiers in immunology · 2016Review
- Modulation of the spleen transcriptome in domestic turkey (Meleagris gallopavo) in response to aflatoxin B1 and probiotics.Immunogenetics · 2015Article
- In vivo maturation of allo-specific CD8 CTL and prevention of lupus-like graft-versus-host disease is critically dependent on T cell signaling through the TNF p75 receptor but not the TNF p55 receptor.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- T cells, murine chronic graft-versus-host disease and autoimmunity.Journal of autoimmunity · 2012Review
- Presentation of hemophagocytic lymphohistiocytosis due to a novel MUNC 13-4 mutation masked by partial therapeutic immunosuppression.Pediatric rheumatology online journal · 2012Article
- Donor CD8 T cells and IFN-gamma are critical for sex-based differences in donor CD4 T cell engraftment and lupus-like phenotype in short-term chronic graft-versus-host disease mice.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Enhancement of suboptimal CD8 cytotoxic T cell effector function in vivo using antigen-specific CD80 defective T cells.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Implications of the parent-into-F1 model for human lupus pathogenesis: roles for cytotoxic T lymphocytes and viral pathogens.Current opinion in rheumatology · 2010Review
- Donor CD8 T cell activation is critical for greater renal disease severity in female chronic graft-vs.-host mice and is associated with increased splenic ICOS(hi) host CD4 T cells and IL-21 expression.Clinical immunology (Orlando, Fla.) · 2010Article
- Advances in lupus stemming from the parent-into-F1 model.Trends in immunology · 2010Review
- Roles of Host Nonhematopoietic Cells in Autoimmunity and Donor Cell Engraftment in Graft-versus-host Disease.Immune network · 2010Article
- Proteasome inhibition and allogeneic hematopoietic stem cell transplantation: a review.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2009Review
- Regulatory T cell (Treg) subsets return in patients with refractory lupus following stem cell transplantation, and TGF-beta-producing CD8+ Treg cells are associated with immunological remission of lupus.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
To determine the role of perforin-mediated cytotoxic T lymphocyte (CTL) effector function in immune regulation, we studied a well-characterized mouse model of graft-versus-host disease (GVHD). Induction of acute GVHD using perforin-deficient donor T cells (pfp-->F1) initially resulted in features of acute GVHD, e.g., engraftment of both donor CD4(+) and CD8(+) T cells, upregulation of Fas and FasL, production of antihost CTL, and secretion of both Th1 and Th2 cytokines. Despite fully functional FasL activity, pfp donor cells failed to totally eliminate host B cells, and, by 4 weeks of disease, cytokine production in pfp-->F1 mice had polarized to a Th2 response. Pfp-->F1 mice eventually developed features of chronic GVHD, such as increased numbers of B cells, persistence of donor CD4 T cells, autoantibody production, and lupuslike renal disease. We conclude that in the setting of B- and T-cell activation, perforin plays an important immunoregulatory role in the prevention of humoral autoimmunity through the elimination of both autoreactive B cells and ag-specific T cells. Moreover, an ineffective initial CTL response can evolve into a persistent antibody-mediated response and, with it, the potential for sustained humoral autoimmunity.
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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.