title: Regulatory Cell Populations in Relapsing-Remitting Multiple Sclerosis (RRMS) Patients: Effect of Disease Activity and Treatment Regimens.
abstract: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) of autoimmune etiology that results from an imbalance between CNS-specific T effector cells and peripheral suppressive mechanisms mediated by regulatory cells (RC). In this research, we collected blood samples from 83 relapsing remitting MS (RRMS) patients and 45 healthy persons (HC), to assess the sizes of their RC populations, including CD4⁺CD25(high)Foxp3⁺ (nTregs), CD3⁺CD4⁺HLA(-)G⁺, CD3⁺CD8⁺CD28(-), CD3⁺CD56⁺, and CD56(bright) cells, and how RC are affected by disease activity (acute phase or remission) and types of treatment (methylprednisolone, interferon, or natalizumab). In addition, we isolated peripheral blood mononuclear cells (PBMC) and cultured them with peptides mapping to myelin antigens, to determine RC responsiveness to autoantigens. The results showed decreased levels of nTregs in patients in the acute phase ± methylprednisolone and in remission + natalizumab, but HC levels in patients in remission or receiving interferon. Patients + interferon had the highest levels of CD3⁺CD4⁺HLA(-)G⁺ and CD3⁺CD8⁺CD28(-) RC, and patients in the acute phase + methylprednisolone the lowest. Patients in remission had the highest levels of CD3⁺CD56⁺, and patients in remission + natalizumab the highest levels of CD56(bright) cells. Only nTregs responded to autoantigens in culture, regardless of disease activity or treatment. The highest suppressive activity was exhibited by nTregs from patients in remission. In conclusion, in RRMS disease activity and type of treatment affect different RC populations. nTregs respond to myelin antigens, indicating that it is possible to restore immunological tolerance through nTreg induction.
authors: Division of Hematology, Department of Internal Medicine, Faculty of Medicine, University of Patras, Patras GR-26500, Greece. marodi_biol@yahoo.gr.
authors: Maria
authors: M
authors: Rodi
authors: Department of Neurology, Faculty of Medicine & University Hospital, University of Patras, Patras GR-26500, Greece. ndimisianos@yahoo.gr.
authors: Nikolaos
authors: N
authors: Dimisianos
authors: Division of Hematology, Department of Internal Medicine, Faculty of Medicine, University of Patras, Patras GR-26500, Greece. delastic@gmail.com.
authors: Anne-Lise
authors: AL
authors: de Lastic
authors: Division of Hematology, Department of Internal Medicine, Faculty of Medicine, University of Patras, Patras GR-26500, Greece. gsakel@upatras.gr.
authors: Panagiota
authors: P
authors: Sakellaraki
authors: Eldrug S.A., Pharmaceutical Company, Platani, Patras GR-26504, Greece. gderaos@upatras.gr.
authors: George
authors: G
authors: Deraos
authors: Eldrug S.A., Pharmaceutical Company, Platani, Patras GR-26504, Greece. imats@upatras.gr.
authors: John
authors: J
authors: Matsoukas
authors: Department of Neurology, Faculty of Medicine & University Hospital, University of Patras, Patras GR-26500, Greece. papat@upatras.gr.
authors: Panagiotis
authors: P
authors: Papathanasopoulos
authors: Division of Hematology, Department of Internal Medicine, Faculty of Medicine, University of Patras, Patras GR-26500, Greece. mouzaki@upatras.gr.
authors: Athanasia
authors: A
authors: Mouzaki
mesh_terms: D000328:Adult; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D004676:Myelin Basic Protein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D000069442:Natalizumab / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D001324:Autoantigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D000069442:Natalizumab; D008775:Methylprednisolone
keywords: HLA-G; MBP; MOG; NKbright; Tregs; iNKT; interferon; methylprednisolone; multiple sclerosis; myelin basic protein; myelin oligodendrocyte glycoprotein; natalizumab