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Feasibility of up-regulating CD4(+)CD25(+) Tregs by IFN-γ in myasthenia gravis patients

BACKGROUND: In myasthenia gravis (MG) patients, the dysfunction of CD4(+)CD25(+) regulatory T cells (CD4(+)CD25(+) Tregs) may be one of the important pathogenesis of MG. Currently, the role of IFN-γ in autoimmune diseases is still controversial and needs further exploration. In this study, whether I...

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Detalles Bibliográficos
Autores principales: Huang, Shuo, Wang, Weizhi, Chi, Lijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562356/
https://www.ncbi.nlm.nih.gov/pubmed/26347149
http://dx.doi.org/10.1186/s12883-015-0419-9
Descripción
Sumario:BACKGROUND: In myasthenia gravis (MG) patients, the dysfunction of CD4(+)CD25(+) regulatory T cells (CD4(+)CD25(+) Tregs) may be one of the important pathogenesis of MG. Currently, the role of IFN-γ in autoimmune diseases is still controversial and needs further exploration. In this study, whether IFN-γ can induce CD4(+)CD25(−) T cells into CD4(+)CD25(+) Tregs in MG in vitro was investigated systematically. METHODS: Flow cytometry was used to analyze the number of CD4(+)CD25(+) Tregs in MG patients and healthy controls (HCs). CD4(+)CD25(−) T cells were separated from the peripheral blood mononuclear cells of MG patients and HCs, and the CD4(+)CD25(+) Tregs were separated from HCs by Magnetic cell sorting (MACS). IFN-γ with different concentrations was used to stimulate CD4(+)CD25(−) T cells. The percentages of the induced CD4(+)CD25(+) T cells were detected by flow cytometry. The FoxP3 expression of the induced CD4(+)CD25(+) T cells in MG patients was detected by real-time PCR at mRNA level. The induced CD4(+)CD25(+) T cells were co-cultured with autologous CD4(+)CD25(−) T cells to estimate the suppressive ability of the induced CD4(+)CD25(+) T cells to CD4(+)CD25(−) T cells. RESULTS: It shows the percentages of CD4(+)CD25(+) T cells among CD4(+) T cells have no significant difference in MG patients compared with those in HCs. There is also merely no difference in the percentages of CD4(+)CD25(+) T cells between thymectomized and non-thymectomized MG patients. CD4(+)CD25(−) T cells can be induced to CD4(+)CD25(+) T cells after applying IFN-γ in MG patients and HCs. The proportion and FoxP3 expression of the induced CD4(+)CD25(+) T cells are the highest at the level of 40 ng/ml IFN-γ, and the suppressive function of the CD4(+)CD25(+) T cells induced by 40 ng/ml IFN-γ is the strongest in MG patients. CONCLUSIONS: This subject will further reveal the role of IFN-γ in the pathogenesis of MG from a new perspective. It will also provide the scientific basis for the clinical targeted therapy of MG.