Research Of Natural T Regulatory Cells And Its Influencing Factors In The Thymomas With Myasthenia Gravis

Myasthenia gravis(MG) is caused by T-cell dependent autoantibodies against muscle acetylcholine receptors(AChR) at the neuromuscular junction.The pathogenesis of MG is involved by many of the relative immune factors.The imbalance of immune system plays an important role in it.Natural occurring regulartory T cells(nTreg) are a group of negative regulatory cells,which have potent ability to suppress the functions of other immune cells.Treg cells express the CD25(interleukin 2 receptor-α),cytotoxic T lymphocyte associated-antigen 4(CTLA-4) and transforming growth factorβ(TGF-β).The forkhead/winged helix transcription factor,FoxP3,was reported recently to be essential for the development and functional activity of Treg cells.CD4~+ CD25~+ Treg cells inhibit the development of autoimmune disorders in rodent models.Despite a growing interest in CD4~+ CD25~+ Treg cells and their role in the emergence of autoimmune diseases in animal medels, only very limited and controversial information is available in the pathogenesis of human autoimmune diseases.Thymic stromal lymphopoietin(TSLP) is an IL-7 like cytokine.TSLP can activate dendritic cells(DC) which induce a robust homeostatic proliferation of naive CD4~+ T cells.MG is the only disease in which the thymus is believed to the initiation organ of pathogenesis and is also characterized by a high incidence of morphologic thymic abnormalities.To find the role of nTregs in pathogenesis of MG,we used immunohistochemical analysis to detect the number of CD4~+FoxP3~+ Treg cells in human thymic sections and used real-time quantitative polymerase chain reaction to detect the FoxP3 mRNA levels and TSLP mRNA levels. We also aimed to find the relationship between FoxP3 and TSLP.Part one:The study of the number of natural occurring regulartory T cells in thymomas from patients with myasthenia gravis.Objective The aim of the study is to observe the CD4~+FoxP3~+ nTreg cells in thymomas from patients with MG compared to those from healthy subjects.Methods The numbers of CD4~+FoxP3~+ nTreg cells of 23 thymomas from patients with MG and 4 healthy controls were detected by immunohistochemical analysis.Results CD4~+ FoxP3~+ nTreg cells in thymomas were significantly decreased compared with normal thymus(P＜0.01);CD4~+FoxP3~+ nTreg cells in B1 organoid thymomas were higher than other types of thymomas,this difference was statistically significant(P＜0.01);the differences between A,B2 and B3 organoid thymomas were not statistically significant(P＞0.05).Conclusions These results revealed that decrease of CD4~+ FoxP3~+ nTreg cells in thymomas from patients with MG.might be related to the pathogenesis of thymomas.Part two:Expression of FoxP3 mRNA and TSLP mRNA in myasthenia gravis.Objective The aim of the study is to detect the expression of FoxP3 mRNA and TSLP mRNA in thymomas from patients with MG compared to those from healthy subjects.Methods The expression of FoxP3 mRNA and TSLP mRNA of 23 thymomas from patients with MG and 4 healthy controls were detected by realtime reverse trancription polymerase chain reaction(realtime RT-PCR).Results Standard values of FoxP3 mRNA and thymic stromal lymphopoietin(TSLP) mRNA were significantly decreased in thymomas(P＜0.01).Standard values of FoxP3 mRNA and TSLP mRNA in B1 organoid thymomas were higher than other types of thymomas,these differences were statistically significant(P＜0.01).The concentration of FoxP3mRNA was positive correlation with the concentration of TSLPmRNA. Conclusions These results suggested that there was decrease of CD4~+FoxP3~+ nTreg cells in thymomas from patients with MG and the decrease transcriptional levels of Foxp 3 may be regulated by decrease transcription of TSLP.The decrease of CD4~+ FoxP3~+ nTreg cells may disturb the immune tolerance of patients with thymomas.