Changes of circulating Tfr and Tfh cells in children with myasthenia gravis
Objective 
To investigate the changes of follicular regulatory T cells (Tfr cells) and follicular T helper cells (Tfh cells) in peripheral blood of children with myasthenia gravis (MG). 
 
 
Methods 
We recruited 28 MG patients and 20 healthy subjects in this study. The percentages of Tfh and Tfr cells in peripheral blood samples were measured by flow cytometry. Real-time PCR was performed to detect the expression of transcription factors and regulatory factors of Bcl-6, c-MAF, Blimp-1 and PD-1 at mRNA level. ELISA was used to detect the levels of IL-2, IL-6, IL-10 and IL-21 in plasma samples and the titers of Ach-Rab and PsMab. 
 
 
Results 
Compared with the healthy subjects, the MG patients showed higher percentages of Tfh cells and lower percentages of Tfr cells before receiving treatment. The expression of Bcl-6 and c-MAF on CD4+ T lymphocytes cells at transcriptional level were significantly enhanced, while the expression of Blimp-1 on CD4+ T cells and the expression of PD-1 on Treg cells at transcriptional level were inhibited in the MG patients in comparison with those in healthy subjects. Moreover, decreased levels of IL-2 and increased levels of IL-21 were found in plasma samples collected from the MG patients. 
 
 
Conclusion 
The decreased percentages of Tfr cells and increased percentages of Tfh cells in patients with MG resulted in abnormal ratios of Tfr/Tfh cells, which might be involved in the immunological pathogenesis of MG. Several changes in the patients with MG might be responsible for the imbalanced ratio of Tfr/Tfh cells, which included changes of IL-2 and IL-21 in microenvironment, enhanced expression of Bcl-6 and c-MAF at mRNA level and inhibited expression of Blimp-1 at mRNA level on CD4+ T cells as well as over-expression of PD-1 at mRNA level on Treg cells. 
 
 
Key words: 
Myasthenia gravis; Tfr cells; Tfh cells