Characterization of CD4+ and CD8+ T Cell Subsets and Interferon Regulatory Factor 4 (IRF4) in MS Patients Treated with Fingolimod (FTY-720): A Follow-up Study

Iranian Journal of Allergy, Asthma and Immunology

Rahimeh Emamnejad¹  Mehdi Shekarabi²  Maryam Izad³  Bahare Laribi⁴  Mohsen Marzban⁵  Shokufeh Sadaghiani⁶  Mohammad Ali Sahraian⁶ 

[1] Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran;Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran;Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran;Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;Department of Neurosciences, Tehran University of Medical Sciences, Tehran, Iran;MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran;

关键词: Fingolimod;    IFN regulatory factor 4;    Multiple sclerosis;    T cell;   

DOI  :  10.18502/ijaai.v17i4.94

来源: DOAJ

【 摘 要 】

Fingolimod is a novel immunomodulatory drug used in patients with relapsing multiple sclerosis (MS) which reversibly inhibits egress of lymphocytes from lymph nodes. In this longitudinal study, the frequency of Interferon- gamma (IFN-γ)+, IL4+, IL17+ and IL10+ CD4+ and CD8+ T cell subsets were measured in Fingolimod treated patients before and after 12 months’(12M) therapy using flow cytometry and compared to those of naive, Betaferon treated MS patients and healthy individuals. Additionally, the level of transcription factor IRF4 and IL-6, IL-23, TGF-β1 cytokines, required for differentiation of IL-17+ T cells, were assessed by RT-PCR and ELISA, respectively. In Fingolimod treated MS patients, we observed a significant decrease in the percentage of IFN-γ+/IL17+ CD4+ and CD8+ T cell subsets. In contrast, Fingolimod increased IL10+ CD4+ T cells. We also showed that IFN-γ+IL17+ co-producing CD8+ T cells were reduced in patients under fingolimod therapy. furthermore, Fingolimod could reduce the expression level of IRF4 in patients while IL6 was increased in the supernatant of cultured peripheral blood mononuclear cells. Our data showed that Fingolimod treatment alters CD4+ and CD8+ T cell subsets and reduces expression of IRF-4, which affects the proportion of pathogenic memory T cells in peripheral blood.

【 授权许可】

Unknown