{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:30:34Z","timestamp":1791163834468,"version":"4.1.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2009,7,1]],"date-time":"2009-07-01T00:00:00Z","timestamp":1246406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>FOXP3-expressing naturally occurring CD4+CD25high T regulatory cells (Treg) are relevant in the control of autoimmunity, and a defect in this cell population has been observed in several human autoimmune diseases. We hypothesized that altered functions of peripheral Treg cells might play a role in the immunopathogenesis of myasthenia gravis, a T cell-dependent autoimmune disease characterized by the presence of pathogenic autoantibodies specific for the nicotinic acetylcholine receptor. We report in this study a significant decrease in the in vitro suppressive function of peripheral Treg cells isolated from myasthenia patients in comparison to those from healthy donors. Interestingly, Treg cells from prednisolone-treated myasthenia gravis patients showed an improved suppressive function compared with untreated patients, suggesting that prednisolone may play a role in the control of the peripheral regulatory network. Indeed, prednisolone treatment prevents LPS-induced maturation of monocyte-derived dendritic cells by hampering the up-regulation of costimulatory molecules and by limiting secretion of IL-12 and IL-23, and enhancing IL-10. In addition, CD4+ T cells cultured in the presence of such tolerogenic dendritic cells are hyporesponsive and can suppress autologous CD4+ T cell proliferation. The results shown in this study indicate that prednisolone treatment promotes an environment that favors immune regulation rather than inflammation.<\/jats:p>","DOI":"10.4049\/jimmunol.0802046","type":"journal-article","created":{"date-parts":[[2009,6,19]],"date-time":"2009-06-19T22:01:30Z","timestamp":1245448890000},"page":"841-848","source":"Crossref","is-referenced-by-count":88,"title":["Prednisolone Treatment Induces Tolerogenic Dendritic Cells and a Regulatory Milieu in Myasthenia Gravis Patients"],"prefix":"10.1093","volume":"183","author":[{"given":"Claudia","family":"Luther","sequence":"first","affiliation":[{"name":"Department of General Neurology and Neurodegenerative Disorders, Hertie Institute for Clinical Brain Research, T\u00fcbingen University Hospital ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Adamopoulou","sequence":"additional","affiliation":[{"name":"Medical Clinic and Policlinic II, Julius-Maximilian University of W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Stoeckle","sequence":"additional","affiliation":[{"name":"Department of General Neurology and Neurodegenerative Disorders, Hertie Institute for Clinical Brain Research, T\u00fcbingen University Hospital ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Brucklacher-Waldert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Rosenkranz","sequence":"additional","affiliation":[{"name":"Department of General Neurology and Neurodegenerative Disorders, Hertie Institute for Clinical Brain Research, T\u00fcbingen University Hospital ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Stoltze","sequence":"additional","affiliation":[{"name":"Department of General Neurology and Neurodegenerative Disorders, Hertie Institute for Clinical Brain Research, T\u00fcbingen University Hospital ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid","family":"Lauer","sequence":"additional","affiliation":[{"name":"Department of General Neurology and Neurodegenerative Disorders, Hertie Institute for Clinical Brain Research, T\u00fcbingen University Hospital ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Poeschel","sequence":"additional","affiliation":[{"name":"Department of General Neurology and Neurodegenerative Disorders, Hertie Institute for Clinical Brain Research, T\u00fcbingen University Hospital ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Melms","sequence":"additional","affiliation":[{"name":"Department of General Neurology and Neurodegenerative Disorders, Hertie Institute for Clinical Brain Research, T\u00fcbingen University Hospital ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Tolosa","sequence":"additional","affiliation":[{"name":"Department of General Neurology and Neurodegenerative Disorders, Hertie Institute for Clinical Brain Research, T\u00fcbingen University Hospital ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,7,15]]},"reference":[{"key":"2026012811270628800_R1","first-page":"5967","article-title":"Autoreactive T cells in healthy individuals.","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012811270628800_R2","first-page":"345","article-title":"Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self.","volume-title":"Nat. Immunol.","year":"2005"},{"key":"2026012811270628800_R3","first-page":"1","article-title":"CD4+CD25+-regulatory T cells from mouse to man.","volume-title":"Scand. J. Immunol.","year":"2005"},{"key":"2026012811270628800_R4","first-page":"190","article-title":"Characterization of human CD25+ CD4+ T cells in thymus, cord and adult blood.","volume-title":"Immunology","year":"2002"},{"key":"2026012811270628800_R5","first-page":"1057","article-title":"Control of regulatory T cell development by the transcription factor Foxp3.","volume-title":"Science","year":"2003"},{"key":"2026012811270628800_R6","first-page":"209","article-title":"FOXP3: of mice and men.","volume-title":"Annu. Rev. Immunol.","year":"2006"},{"key":"2026012811270628800_R7","first-page":"1142","article-title":"A function for interleukin 2 in Foxp3-expressing regulatory T cells.","volume-title":"Nat. Immunol.","year":"2005"},{"key":"2026012811270628800_R8","first-page":"83","article-title":"Isolation, expansion, and characterization of human natural and adaptive regulatory T cells.","volume-title":"Methods Mol. Biol.","year":"2007"},{"key":"2026012811270628800_R9","first-page":"477","article-title":"Immature, but not inactive: the tolerogenic function of immature dendritic cells.","volume-title":"Immunol. Cell Biol.","year":"2002"},{"key":"2026012811270628800_R10","first-page":"127","article-title":"Pharmacological induction of tolerogenic dendritic cells and regulatory T cells.","volume-title":"Semin. Immunol.","year":"2004"},{"key":"2026012811270628800_R11","first-page":"S109","article-title":"T-regulatory 1 cells: a novel subset of CD4 T cells with immunoregulatory properties.","volume-title":"J. Allergy Clin. Immunol.","year":"2000"},{"key":"2026012811270628800_R12","first-page":"6323","article-title":"The regulatory T cell family: distinct subsets and their interrelations.","volume-title":"J. Immunol.","year":"2003"},{"key":"2026012811270628800_R13","first-page":"351","article-title":"Regulatory T cells: development, function and role in autoimmunity.","volume-title":"Autoimmun. Rev.","year":"2005"},{"key":"2026012811270628800_R14","first-page":"92","article-title":"Control of immune pathology by regulatory T cells.","volume-title":"Novartis Found. Symp.","year":"2003"},{"key":"2026012811270628800_R15","first-page":"971","article-title":"Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis.","volume-title":"J. Exp. Med.","year":"2004"},{"key":"2026012811270628800_R16","first-page":"131","article-title":"Multiple immuno-regulatory defects in type-1 diabetes.","volume-title":"J. Clin. Invest.","year":"2002"},{"key":"2026012811270628800_R17","first-page":"92","article-title":"Defective suppressor function in CD4+CD25+ T-cells from patients with type 1 diabetes.","volume-title":"Diabetes","year":"2005"},{"key":"2026012811270628800_R18","first-page":"215","article-title":"Isolation and functional characterization of regulatory CD25brightCD4+ T cells from the target organ of patients with rheumatoid arthritis.","volume-title":"Eur. J. Immunol.","year":"2003"},{"key":"2026012811270628800_R19","first-page":"797","article-title":"Unravelling the pathogenesis of myasthenia gravis.","volume-title":"Nat. Rev. Immunol.","year":"2002"},{"key":"2026012811270628800_R20","first-page":"902","article-title":"Thymus in myasthenia gravis: isolation of T-lymphocyte lines specific for the nicotinic acetylcholine receptor from thymuses of myasthenic patients.","volume-title":"J. Clin. Invest.","year":"1988"},{"key":"2026012811270628800_R21","first-page":"393","article-title":"Anti-acetylcholine receptor antibody synthesis by cultured lymphocytes in myasthenia gravis: thymic and peripheral blood cell interactions.","volume-title":"Ann. NY Acad. Sci.","year":"1981"},{"key":"2026012811270628800_R22","first-page":"2122","article-title":"Myasthenia gravis.","volume-title":"Lancet","year":"2001"},{"key":"2026012811270628800_R23","first-page":"4081","article-title":"Novel mechanism for inhibition of human T cells by glucocorticoids: glucocorticoids inhibit signal transduction through IL-2 receptor.","volume-title":"J. Immunol.","year":"1993"},{"key":"2026012811270628800_R24","first-page":"1342","article-title":"Inhibition of human dendritic cell functions by methylprednisolone.","volume-title":"Transplantation","year":"1999"},{"key":"2026012811270628800_R25","first-page":"124","article-title":"Decreased frequency of intrathymic regulatory T cells in patients with myasthenia-associated thymoma.","volume-title":"J. Neuroimmunol.","year":"2005"},{"key":"2026012811270628800_R26","first-page":"735","article-title":"Functional defect of regulatory CD4+CD25+ T cells in the thymus of patients with autoimmune myasthenia gravis.","volume-title":"Blood","year":"2005"},{"key":"2026012811270628800_R27","first-page":"4180","article-title":"Cutting edge: direct suppression of B cells by CD4+ CD25+ regulatory T cells.","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012811270628800_R28","first-page":"394","article-title":"Dendritic cells as a tool to induce anergic and regulatory T cells.","volume-title":"Trends Immunol.","year":"2001"},{"key":"2026012811270628800_R29","first-page":"330","article-title":"Foxp3 programs the development and function of CD4+CD25+ regulatory T cells.","volume-title":"Nat. Immunol.","year":"2003"},{"key":"2026012811270628800_R30","first-page":"744","article-title":"Immune dysregulation, polyendocrinopathy, enteropathy: X-linked: forkhead box protein 3 mutations and lack of regulatory T cells.","volume-title":"J. Allergy Clin. Immunol.","year":"2007"},{"key":"2026012811270628800_R31","first-page":"112","article-title":"IPEX, FOXP3 and regulatory T-cells: a model for autoimmunity.","volume-title":"Immunol. Res.","year":"2007"},{"key":"2026012811270628800_R32","first-page":"117","article-title":"Higher frequency of regulatory T cells in the elderly and increased suppressive activity in neurodegeneration.","volume-title":"J. Neuroimmunol.","year":"2007"},{"key":"2026012811270628800_R33","first-page":"345","article-title":"Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production.","volume-title":"Int. Immunol.","year":"2007"},{"key":"2026012811270628800_R34","first-page":"2983","article-title":"Induction of FOXP3 expression in naive human CD4+ FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-\u03b2 dependent but does not confer a regulatory phenotype.","volume-title":"Blood","year":"2007"},{"key":"2026012811270628800_R35","first-page":"3276","article-title":"The role of 2 FOXP3 isoforms in the generation of human CD4+ Tregs.","volume-title":"J. Clin. Invest.","year":"2005"},{"key":"2026012811270628800_R36","first-page":"1198","article-title":"Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates.","volume-title":"Ann. Intern. Med.","year":"1993"},{"key":"2026012811270628800_R37","first-page":"1807","article-title":"The effect of calcineurin inhibitors and corticosteroids on the differentiation of human dendritic cells.","volume-title":"Eur. J. Immunol.","year":"2000"},{"key":"2026012811270628800_R38","first-page":"23","article-title":"Molecular mechanisms and Th1\/Th2 pathways in corticosteroid regulation of cytokine production.","volume-title":"J. Neuroimmunol.","year":"2000"},{"key":"2026012811270628800_R39","first-page":"373","article-title":"Therapeutic options in autoimmune myasthenia gravis.","volume-title":"Autoimmun. Rev.","year":"2007"},{"key":"2026012811270628800_R40","first-page":"419","article-title":"Taking dendritic cells into medicine.","volume-title":"Nature","year":"2007"},{"key":"2026012811270628800_R41","first-page":"S53","article-title":"Dendritic cells: understanding immunogenicity.","volume-title":"Eur. J. Immunol.","year":"2007"},{"key":"2026012811270628800_R42","first-page":"174","article-title":"Antigen-bearing immature dendritic cells induce peptide-specific CD8+ regulatory T cells in vivo in humans.","volume-title":"Blood","year":"2002"},{"key":"2026012811270628800_R43","first-page":"1213","article-title":"Induction of interleukin 10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells.","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2026012811270628800_R44","first-page":"6473","article-title":"Glucocorticoids affect human dendritic cell differentiation and maturation.","volume-title":"J. Immunol.","year":"1999"},{"key":"2026012811270628800_R45","first-page":"1233","article-title":"Differential effects of corticosteroids during different stages of dendritic cell maturation.","volume-title":"Eur. J. Immunol.","year":"2000"},{"key":"2026012811270628800_R46","first-page":"185","article-title":"Cytokine-based immunointervention in the treatment of autoimmune diseases.","volume-title":"Clin. Exp. Immunol.","year":"2003"},{"key":"2026012811270628800_R47","first-page":"96","article-title":"IL-12 and IL-23: master regulators of innate and adaptive immunity.","volume-title":"Immunol. Rev.","year":"2004"},{"key":"2026012811270628800_R48","first-page":"45","article-title":"Dexamethasone induces IL-10-producing monocyte-derived dendritic cells with durable immaturity.","volume-title":"Scand. J. Immunol.","year":"2005"},{"key":"2026012811270628800_R49","first-page":"357","article-title":"Influence of immunosuppressive drugs on dendritic cells.","volume-title":"Transpl. Immunol.","year":"2003"},{"key":"2026012811270628800_R50","first-page":"947","article-title":"Oral tolerance: immune mechanisms and the generation of Th3-type TGF-\u03b2-secreting regulatory cells.","volume-title":"Microbes Infect.","year":"2001"},{"key":"2026012811270628800_R51","first-page":"1875","article-title":"Conversion of peripheral CD4+CD25\u2212 naive T cells to CD4+CD25+ regulatory T cells by TGF-\u03b2 induction of transcription factor Foxp3.","volume-title":"J. Exp. Med.","year":"2003"},{"key":"2026012811270628800_R52","first-page":"603","article-title":"In vitro generation of interleukin 10-producing regulatory CD4+ T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines.","volume-title":"J. Exp. Med.","year":"2002"},{"key":"2026012811270628800_R53","first-page":"1162","article-title":"Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells.","volume-title":"Blood","year":"2005"},{"key":"2026012811270628800_R54","first-page":"15770","article-title":"NCX-1015, a nitric-oxide derivative of prednisolone, enhances regulatory T cells in the lamina propria and protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2002"},{"key":"2026012811270628800_R55","first-page":"568","article-title":"HLA-G expression defines a novel regulatory T-cell subset present in human peripheral blood and sites of inflammation.","volume-title":"Blood","year":"2007"},{"key":"2026012811270628800_R56","first-page":"925","article-title":"Is FOXP3 a bona fide marker for human regulatory T cells?.","volume-title":"Eur. J. Immunol.","year":"2008"},{"key":"2026012811270628800_R57","first-page":"6659","article-title":"Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2006"},{"key":"2026012811270628800_R58","first-page":"5986","article-title":"IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells.","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012811270628800_R59","first-page":"605","article-title":"Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo.","volume-title":"Immunity","year":"2003"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/183\/2\/841\/62694397\/9293.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/183\/2\/841\/62694397\/9293.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T16:30:03Z","timestamp":1769617803000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/183\/2\/841\/8053621"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,7]]},"references-count":59,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2009,7,15]]},"published-print":{"date-parts":[[2009,7,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0802046","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,7]]},"published":{"date-parts":[[2009,7]]}}}