{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T17:45:38Z","timestamp":1788198338506,"version":"build-2803163510"},"reference-count":61,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2015,7,17]],"date-time":"2015-07-17T00:00:00Z","timestamp":1437091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DFG single grant","award":["GR3946\/2_1"],"award-info":[{"award-number":["GR3946\/2_1"]}]},{"name":"DFG Transregio 128","award":["TRR128\/1,A09"],"award-info":[{"award-number":["TRR128\/1,A09"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple sclerosis (MS) is an inflammatory autoimmune disease characterized by imbalanced immune regulatory networks, and MS patient-derived T effector cells are inefficiently suppressed through regulatory T cells (Treg), a phenomenon known as Treg resistance. In the current study we investigated T cell function in MS patients before  and after interferon-beta therapy. We compared cytokine profile, responsiveness for  Treg-mediated suppression ex vivo and evaluated reactivity of T cells in vivo using  a humanized mouse model. We found that CD4+ and CD8+ T cells of therapy-naive MS patients were resistant to Treg-mediated suppression. Treg resistance is associated with  an augmented IL-6 production, enhanced IL-6 receptor expression, and increased  PKB\/c-Akt phosphorylation. These parameters as well as responsiveness of T cells to Treg-mediated suppression were restored after interferon-beta therapy of MS patients. Following transfer into immunodeficient mice, MS T cells induced a lethal graft versus host disease (GvHD) and in contrast to T cells of healthy volunteers, this aggressive T cell response could not be controlled by Treg, but was abolished by anti-IL-6 receptor antibodies. However, magnitude and lethality of GvHD induced by MS T cells was significantly decreased after interferon-beta therapy and the reaction was prevented by Treg activation in vivo. Our data reveals that interferon-beta therapy improves the immunoregulation of autoaggressive T effector cells in MS patients by changing the IL-6 signal transduction pathway, thus restoring their sensitivity to Treg-mediated suppression.<\/jats:p>","DOI":"10.3390\/ijms160716330","type":"journal-article","created":{"date-parts":[[2015,7,17]],"date-time":"2015-07-17T11:18:48Z","timestamp":1437131928000},"page":"16330-16346","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Interferon-Beta Therapy of Multiple Sclerosis Patients Improves the Responsiveness of T Cells for Immune Suppression by Regulatory T Cells"],"prefix":"10.3390","volume":"16","author":[{"given":"Bettina","family":"Trinschek","sequence":"first","affiliation":[{"name":"Department of Dermatology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstr. 1, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Luessi","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstr. 1, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina","family":"Gross","sequence":"additional","affiliation":[{"name":"Department of Neurology-Inflammatory Disorders of the Nervous System and Neurooncology, University of Muenster, Schlossplatz 2, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Wiendl","sequence":"additional","affiliation":[{"name":"Department of Neurology-Inflammatory Disorders of the Nervous System and Neurooncology, University of Muenster, Schlossplatz 2, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Jonuleit","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstr. 1, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/ncpneuro0832","article-title":"The role of regulatory T cells in multiple sclerosis","volume":"4","author":"Zozulya","year":"2008","journal-title":"Nat. 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