دورية أكاديمية
Methotrexate treatment affects effector but not regulatory T cells in juvenile idiopathic arthritis.
| العنوان: | Methotrexate treatment affects effector but not regulatory T cells in juvenile idiopathic arthritis. |
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| المؤلفون: | Bulatović Ćalasan M; Center for Molecular and Cellular Intervention, Department of Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands m.bulatovic@umcutrecht.nl., Vastert SJ; Center for Molecular and Cellular Intervention, Department of Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands., Scholman RC; Center for Molecular and Cellular Intervention, Department of Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands., Verweij F; Center for Molecular and Cellular Intervention, Department of Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands., Klein M; Center for Molecular and Cellular Intervention, Department of Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands., Wulffraat NM; Center for Molecular and Cellular Intervention, Department of Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands., Prakken BJ; Center for Molecular and Cellular Intervention, Department of Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands., van Wijk F; Center for Molecular and Cellular Intervention, Department of Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands. |
| المصدر: | Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2015 Sep; Vol. 54 (9), pp. 1724-34. Date of Electronic Publication: 2015 Apr 14. |
| نوع المنشور: | Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 100883501 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1462-0332 (Electronic) Linking ISSN: 14620324 NLM ISO Abbreviation: Rheumatology (Oxford) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford, UK : Avenel, N.J. : Oxford University Press ; Distributed by Mercury International, c1999- |
| مواضيع طبية MeSH: | Antirheumatic Agents/*pharmacology , Arthritis, Juvenile/*pathology , Cell Proliferation/*drug effects , Methotrexate/*pharmacology , T-Lymphocyte Subsets/*drug effects , T-Lymphocytes, Regulatory/*drug effects, Adolescent ; Antirheumatic Agents/therapeutic use ; Arthritis, Juvenile/drug therapy ; Arthritis, Juvenile/metabolism ; Cells, Cultured ; Child ; Child, Preschool ; Cytokines/metabolism ; Dose-Response Relationship, Drug ; Female ; Follow-Up Studies ; Humans ; Immunity/drug effects ; Interferon-gamma/blood ; Male ; Methotrexate/therapeutic use ; Phenotype ; Prospective Studies ; T-Lymphocyte Subsets/metabolism ; T-Lymphocyte Subsets/pathology ; T-Lymphocytes, Regulatory/metabolism ; T-Lymphocytes, Regulatory/pathology ; Treatment Outcome |
| مستخلص: | Objective: The balance between Treg and effector T cells (Teff) is crucial for immune regulation in JIA. How MTX, the cornerstone treatment in JIA, influences this balance in vivo is poorly elucidated. The aim of this study was to investigate quantitative and qualitative effects of MTX on Treg and Teff in JIA patients during MTX treatment. Methods: Peripheral blood samples were obtained from JIA patients at the start of MTX and 3 and 6 months thereafter. Treg numbers and phenotypes were determined by flow cytometry and suppressive function in allogeneic suppression assays. Teff proliferation upon stimulation with anti-CD3, activation status and intracellular cytokine production were determined by flow cytometry. Effector cell responsiveness to suppression was investigated in autologous suppression assays. Effector cell cytokines in supernatants of proliferation and suppression assays and in plasma were measured by cytokine multiplex assay. Results: MTX treatment in JIA did not affect Treg phenotype and function. Instead, MTX treatment enhanced, rather than diminished, CD4(+) and CD8(+) T cell proliferation of JIA patients after 6 months of therapy, independent of clinical response. Effector cells during MTX treatment were equally responsive to Treg-mediated suppression. MTX treatment did not attenuate Teff activation status and their capacity to produce IL-13, IL-17, TNF-α and IFN-γ. Similarly to Teff proliferation, plasma IFN-γ concentrations after 6 months were increased. Conclusion: This study provides the novel insight that MTX treatment in JIA does not attenuate Teff function but, conversely, enhances T cell proliferation and IFN-γ plasma concentrations in JIA patients. (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.) |
| فهرسة مساهمة: | Keywords: cytokines; effector T cells; juvenile idiopathic arthritis; methotrexate; regulatory T cells; suppression assays |
| المشرفين على المادة: | 0 (Antirheumatic Agents) 0 (Cytokines) 82115-62-6 (Interferon-gamma) YL5FZ2Y5U1 (Methotrexate) |
| تواريخ الأحداث: | Date Created: 20150417 Date Completed: 20151124 Latest Revision: 20150815 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1093/rheumatology/kev101 |
| PMID: | 25877908 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1462-0332 |
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| DOI: | 10.1093/rheumatology/kev101 |