Abstract
BackgroundIn 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.MethodsFlow 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.ResultsIt 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.ConclusionsThis 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.
Highlights
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
The first part of our study mainly showed that the number of CD4+CD25+ T cells in MG patients has no statistical difference from the number of healthy controls (HCs), but the function of them was seriously destroyed, which is consistent with the results of Luther and his colleagues
Frequencies of CD4+CD25+ Tregs in peripheral blood from MG patients In our experiment, Tregs were identified as CD4+CD25high T cells by selecting those CD4+ cells whose CD25 expression exceeded the level of CD25 positivity observed on the CD4 negative population [19]
Summary
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. The role of IFN-γ in autoimmune diseases is still controversial and needs further exploration. Myasthenia gravis (MG) is an autoimmune disorder characterized by muscle weakness and chronic fatigue, which results from a blockage of the nerve impulse transmission from nerve endings to muscles by anti-acetylcholine receptor (AchR) antibodies at the neuromuscular junction. The results may suggest one important way to further overcome the other autoimmune diseases. As the most important regulatory T cells, CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs) were firstly defined by Sakaguchi in 1995 and they are characterized by expressing the chain of IL-2 receptor alpha (CD25) and fork head transcription factor 3 (FoxP3) [1].
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