Regulatory Cell Populations in Relapsing-Remitting Multiple Sclerosis (RRMS) Patients: Effect of Disease Activity and Treatment Regimens

International Journal of Molecular Sciences

Anne-Lise de Lastic¹  Athanasia Mouzaki²  Nikolaos Dimisianos²  Maria Rodi³  Panagiota Sakellaraki³  George Deraos³  Panagiotis Papathanasopoulos⁴  John Matsoukas⁴ 

[1] University Hospital, University of Patras, Patras GR-26500, Greece;;Department of Neurology, Faculty of Medicine &Division of Hematology, Department of Internal Medicine, Faculty of Medicine, University of Patras, Patras GR-26500, Greece;Eldrug S.A., Pharmaceutical Company, Platani, Patras GR-26504, Greece;

关键词: multiple sclerosis;    Tregs;    HLA-G;    iNKT;    NKbright;    methylprednisolone;    natalizumab;    interferon;    myelin oligodendrocyte glycoprotein;    MOG;    myelin basic protein;    MBP;   

DOI  :  10.3390/ijms17091398

来源: DOAJ

【 摘 要 】

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+CD25highFoxp3+ (nTregs), CD3+CD4+HLA−G+, CD3+CD8+CD28−, CD3+CD56+, and CD56bright 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 CD56bright 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.

【 授权许可】

Unknown