دورية أكاديمية
Regulatory T cells inhibit autoantigen-specific CD4 + T cell responses in lupus-prone NZB/W F1 mice.
| العنوان: | Regulatory T cells inhibit autoantigen-specific CD4 + T cell responses in lupus-prone NZB/W F1 mice. |
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| المؤلفون: | Rosenberger S; Department of Rheumatology and Clinical Immunology, Charité - University Medicine, Berlin, Germany.; Helios Dr. Horst Schmidt Kliniken Wiesbaden, Department of General and Visceral Surgery, Wiesbaden, Germany., Undeutsch R; Department of Rheumatology and Clinical Immunology, Charité - University Medicine, Berlin, Germany.; German Rheumatism Research Center (DRFZ), A Leibniz Institute, Berlin, Germany., Akbarzadeh R; Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany., Ohmes J; Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany., Enghard P; German Rheumatism Research Center (DRFZ), A Leibniz Institute, Berlin, Germany.; Department of Nephrology and Intensive Care Medicine, Charité - University Medicine, Berlin, Germany., Riemekasten G; Department of Rheumatology and Clinical Immunology, Charité - University Medicine, Berlin, Germany.; Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany., Humrich JY; Department of Rheumatology and Clinical Immunology, Charité - University Medicine, Berlin, Germany.; Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany. |
| المصدر: | Frontiers in immunology [Front Immunol] 2023 Nov 10; Vol. 14, pp. 1254176. Date of Electronic Publication: 2023 Nov 10 (Print Publication: 2023). |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | T-Lymphocytes, Regulatory* , Lupus Erythematosus, Systemic*, Animals ; Mice ; Autoantigens ; Mice, Inbred NZB ; Autoimmunity |
| مستخلص: | Introduction: Progressive loss of regulatory T cell (Treg)-mediated control over autoreactive effector T cells contributes to the development of systemic lupus erythematosus (SLE). Accordingly, we hypothesized that Treg may also have the capacity to suppress the activation of autoreactive CD4 + T cells that are considered to drive autoimmunity. Methods: To investigate whether Treg are involved in the control of autoreactive CD4 + T cells, we depleted CD25 + Treg cells either in vivo or in vitro , or combined both approaches before antigen-specific stimulation with the SLE-associated autoantigen SmD1(83-119) in the NZB/W F1 mouse model either after immunization against SmD1(83-119) or during spontaneous disease development. Frequencies of autoantigen-specific CD4 + T cells were determined by flow cytometry using the activation marker CD154. Results: Both in vitro and in vivo depletion of CD25 + Treg, respectively, increased the frequencies of detectable autoantigen-specific CD4 + T cells by approximately 50%. Notably, the combined in vivo and in vitro depletion of CD25 + Treg led almost to a doubling in their frequencies. Frequencies of autoantigen-specific CD4 + T cells were found to be lower in immunized haploidentical non-autoimmune strains and increased frequencies were detectable in unmanipulated NZB/W F1 mice with active disease. In vitro re-addition of CD25 + Treg after Treg depletion restored suppression of autoantigen-specific CD4 + T cell activation. Discussion: These results suggest that the activation and expansion of autoantigen-specific CD4 + T cells are partly controlled by Treg in murine lupus. Depletion of Treg therefore can be a useful approach to increase the detectability of autoantigen-specific CD4 + T cells allowing their detailed characterization including lineage determination and epitope mapping and their sufficient ex vivo isolation for cell culture. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Rosenberger, Undeutsch, Akbarzadeh, Ohmes, Enghard, Riemekasten and Humrich.) |
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| فهرسة مساهمة: | Keywords: autoantigen-specific T cells; autoimmunity; immune regulation; lupus; regulatory T cells |
| المشرفين على المادة: | 0 (Autoantigens) |
| تواريخ الأحداث: | Date Created: 20231129 Date Completed: 20231201 Latest Revision: 20240320 |
| رمز التحديث: | 20240321 |
| مُعرف محوري في PubMed: | PMC10667723 |
| DOI: | 10.3389/fimmu.2023.1254176 |
| PMID: | 38022661 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2023.1254176 |