ArticleThe Journal of clinical investigation1997
Evidence that calcineurin is rate-limiting for primary human lymphocyte activation.
Article in The Journal of clinical investigation, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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
11 citing papers in PubMed.
- Immunosuppressive Therapy in Pediatric Kidney Transplantation: Evolution, Current Practices, and Future Directions.Biomedicines · 2025Article
- Quantifying MHC dextramer-induced NFAT activation in antigen-specific T cells as a functional response parameter.Methods (San Diego, Calif.) · 2017Article
- Activation of the vitamin D receptor selectively interferes with calcineurin-mediated inflammation: a clinical evaluation in the abdominal aortic aneurysm.Laboratory investigation; a journal of technical methods and pathology · 2016Article
- Update on pathogenesis and predictors of response of therapeutic strategies used in inflammatory bowel disease.World journal of gastroenterology · 2015Review
- Nuclear translocation of nuclear factor of activated T cells (NFAT) as a quantitative pharmacodynamic parameter for tacrolimus.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2013Article
- Article
- T-cell receptor-stimulated calcineurin activity is inhibited in isolated T cells from transplant patients.The Journal of pharmacology and experimental therapeutics · 2009Article
- Localisation of high acid phosphotyrosine phosphatase activity in afferent arterioles and glomeruli of human kidney.Journal of molecular histology · 2005Article
- Circulating levels of cyclosporin A in inflammatory bowel disease: relationships with lymphocyte inhibition and the age of patients.European journal of clinical pharmacology · 2004Article
- Role of T cells and gamma interferon during induction of hypersensitivity to lipopolysaccharide by toxic shock syndrome toxin 1 in mice.Infection and immunity · 2001Article
- Review
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclosporine (CsA) is both a clinical immunosuppressive drug and a probe to dissect intracellular signaling pathways. In vitro, CsA inhibits lymphocyte gene activation by inhibiting the phosphatase activity of calcineurin (CN). In clinical use, CsA treatment inhibits 50-75% of CN activity in circulating leukocytes. We modeled this degree of CN inhibition in primary human leukocytes in vitro in order to study the effect of partial CN inhibition on the downstream signaling events that lead to gene activation. In CsA-treated leukocytes stimulated by calcium ionophore, the degree of reduction in CN activity was accompanied by a similar degree of inhibition of each event tested: dephosphorylation of nuclear factor of activated T cell proteins, nuclear DNA binding, activation of a transfected reporter gene construct, IFN-gamma and IL-2 mRNA accumulation, and IFN-gamma production. Furthermore, the degree of CN inhibition was reflected by a similar degree of reduction in lymphocyte proliferation and IFN-gamma production in the allogeneic mixed lymphocyte cultures. These data support the conclusion that CN activity is rate-limiting for the activation of primary human T lymphocytes. Thus, the reduction of CN activity observed in CsA-treated patients is accompanied by a similar degree of reduction in lymphocyte gene activation, and accounts for the immunosuppression observed.
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