title: Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis.
abstract: Immunoregulatory T cells of (CD4+)CD25+ phenotype suppress T cell function and protect rodents from organ-specific autoimmune disease. The human counterpart of this subset of T cells expresses high levels of CD25 and its role in human autoimmune disorders is currently under intense investigation. In multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), the activation of circulating self-reactive T cells with specificity for myelin components is considered to be an important disease initiating event. Here, we investigated whether MS is associated with an altered ability of (CD4+)CD25high regulatory T cells (Treg) to confer suppression of myelin-specific immune responses. Whereas Treg frequencies were equally distributed in blood and cerebrospinal fluid of MS patients and did not differ compared to healthy controls, the suppressive potency of patient-derived (CD4+)CD25high T lymphocytes was impaired. Their inhibitory effect on antigen-specific T cell proliferation induced by human recombinant myelin oligodendrocyte protein as well as on immune responses elicited by polyclonal and allogeneic stimuli was significantly reduced compared to healthy individuals. The effect was persistent and not due to responder cell resistance or altered survival of Treg, suggesting that a defective immunoregulation of peripheral T cells mediated by (CD4+)CD25high T lymphocytes promotes CNS autoimmunity in MS.
authors.affiliation: Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Haas
authors.forename: Andreas
authors.initials: A
authors.lastname: Hug
authors.forename: Andrea
authors.initials: A
authors.lastname: Viehöver
authors.forename: Benedikt
authors.initials: B
authors.lastname: Fritzsching
authors.forename: Christine S
authors.initials: CS
authors.lastname: Falk
authors.forename: Andrea
authors.initials: A
authors.lastname: Filser
authors.forename: Tina
authors.initials: T
authors.lastname: Vetter
authors.forename: Linda
authors.initials: L
authors.lastname: Milkova
authors.forename: Mirjam
authors.initials: M
authors.lastname: Korporal
authors.forename: Brigitte
authors.initials: B
authors.lastname: Fritz
authors.forename: Brigitte
authors.initials: B
authors.lastname: Storch-Hagenlocher
authors.forename: Peter H
authors.initials: PH
authors.lastname: Krammer
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Suri-Payer
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wildemann
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000276:immunology; D018791:CD4 Lymphocyte Count; D016923:Cell Death / Q000276:immunology; D049109:Cell Proliferation; D002555:Cerebrospinal Fluid / Q000166:cytology; D018920:Coculture Techniques; D006801:Humans; D018189:Immunomagnetic Separation; D007376:Interleukin-2 / Q000502:physiology; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000276:immunology* / Q000473:pathology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D012075:Remission, Spontaneous; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D007376:Interleukin-2; C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D015375:Receptors, Interleukin-2