دورية أكاديمية
Self-Sustained Resistance to Suppression of CD8+ Teff Cells at the Site of Autoimmune Inflammation Can Be Reversed by Tumor Necrosis Factor and Interferon-γ Blockade.
| العنوان: | Self-Sustained Resistance to Suppression of CD8+ Teff Cells at the Site of Autoimmune Inflammation Can Be Reversed by Tumor Necrosis Factor and Interferon-γ Blockade. |
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| المؤلفون: | Petrelli A; University Medical Center Utrecht, Utrecht, The Netherlands., Wehrens EJ; University Medical Center Utrecht, Utrecht, The Netherlands., Scholman RC; University Medical Center Utrecht, Utrecht, The Netherlands., Prakken BJ; University Medical Center Utrecht, Utrecht, The Netherlands., Vastert SJ; University Medical Center Utrecht, Utrecht, The Netherlands., van Wijk F; University Medical Center Utrecht, Utrecht, The Netherlands. |
| المصدر: | Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2016 Jan; Vol. 68 (1), pp. 229-36. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley Country of Publication: United States NLM ID: 101623795 Publication Model: Print Cited Medium: Internet ISSN: 2326-5205 (Electronic) Linking ISSN: 23265191 NLM ISO Abbreviation: Arthritis Rheumatol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Malden, MA : Wiley, [2014]- |
| مواضيع طبية MeSH: | Arthritis, Juvenile/*immunology , CD8-Positive T-Lymphocytes/*immunology , Cytokines/*immunology , Interferon-gamma/*immunology , Tumor Necrosis Factor-alpha/*immunology, Adolescent ; Antigen-Presenting Cells ; Autoimmune Diseases ; CD4-Positive T-Lymphocytes ; Case-Control Studies ; Cell Proliferation ; Child ; Female ; Flow Cytometry ; Humans ; Inflammation ; Interferon-gamma/antagonists & inhibitors ; Interleukin-10/immunology ; Interleukin-17/immunology ; Interleukin-6/immunology ; Male ; Synovial Fluid/cytology ; T-Lymphocytes, Regulatory ; Tumor Necrosis Factor-alpha/antagonists & inhibitors |
| مستخلص: | Objective: Resistance of Teff cells to Treg cell-mediated suppression contributes to the breakdown of peripheral tolerance in the inflamed joints of patients with juvenile idiopathic arthritis (JIA). However, unanswered questions are whether this resistant phenotype is self-sustained and whether CD8+ and CD4+ Teff cells share the same mechanism of resistance to suppression. We undertook this study to investigate intrinsic resistance of CD8+ Teff cells to suppression and to determine how this can be targeted therapeutically. Methods: CD8+ or CD4+ Teff cells were cultured with or without antigen-presenting cells (APCs) in Treg cell-dependent and -independent suppression assays. Synovial fluid (SF)-derived Teff cells were crosscultured with peripheral blood (PB) Treg cells from JIA patients or healthy controls. Tumor necrosis factor (TNF) or interferon-γ (IFNγ) blocking agents were used to restore Teff cell responsiveness to suppression. Results: Suppression of cell proliferation and cytokine production in CD8+ Teff cells from the SF of JIA patients was severely impaired compared to that in CD8+ Teff cells from the PB of JIA patients, regardless of the presence of APCs and CD4+ Teff cells. Similar to CD4+ Teff cells, impaired suppression of CD8+ Teff cells was shown to be an intrinsic feature of this cell population. While TNF blockade restored both CD8+ and CD4+ Teff cell susceptibility to suppression, autocrine release of IFNγ selectively sustained CD8+ Teff cell resistance, which could be relieved by IFNγ blockade. Conclusion: Unlike CD4+ Teff cells, resistance of CD8+ Teff cells to suppression at the site of autoimmune inflammation is maintained by autocrine release of IFNγ, and blockade of IFNγ restores CD8+ Teff cell responsiveness to suppression. These findings indicate a potential therapeutic value of blocking IFNγ to restore immune regulation in JIA. (© 2016, American College of Rheumatology.) |
| المشرفين على المادة: | 0 (Cytokines) 0 (IL10 protein, human) 0 (IL6 protein, human) 0 (Interleukin-17) 0 (Interleukin-6) 0 (TNF protein, human) 0 (Tumor Necrosis Factor-alpha) 130068-27-8 (Interleukin-10) 82115-62-6 (Interferon-gamma) |
| تواريخ الأحداث: | Date Created: 20150912 Date Completed: 20160503 Latest Revision: 20160511 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1002/art.39418 |
| PMID: | 26360332 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2326-5205 |
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| DOI: | 10.1002/art.39418 |