Circulating regulatory T cells in patients with severe fever with thrombocytopenia syndrome

Abstract

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease caused by SFTS virus (SFTSV). Immunologic factors have been proved to be related to the occurrence and development of SFTS; however, their role still remains to be further elucidated. Methods: Samples from 30 patients with laboratory-confirmed SFTS and 15 healthy controls were subjected to flow cytometry to detect the proportion of CD4+/total lymphocytes, CD4 + CD25+/CD4 + cells and CD4 + CD25+ Foxp3+/CD4 + CD25+ cells in circulating blood and to evaluate their potential function in the development of SFTS. Results: The data showed that a reduced proportion of CD4+/total lymphocytes and CD4 + CD25+/CD4 + cells was observed in patients with SFTS compared with healthy controls. In contrast, the percentage of CD4 + CD25+ Foxp3+/CD4 + CD25+ cells in the patients in the SFTS group was significantly elevated. Furthermore, we investigated the dynamic changes of the circulating regulatory T cells (Tregs) in patients with SFTS at different stages. The results showed that the proportion of CD4+/total lymphocytes and CD4 + CD25+/CD4 + cells in the non-severe group was prominently higher than that in patients with severe SFTS. Conversely, the proportion of CD4 + CD25+ Foxp3+/CD4 + CD25+ cells was lower in the non-severe group than in the severe group. Additionally, the circulating Tregs reverted to normal ranges during the convalescent phase of SFTSV infection. Moreover, the Tregs level correlated with various clinical parameters. Conclusion: We demonstrated that SFTSV infection resulted in a robust circulating Treg response in patients with SFTS. Our investigation suggested that the proportions of CD4+/total lymphocytes and CD4 + CD25+ Foxp3+/CD4 + CD25+ cells in circulating blood could serve as sensitive indices to evaluate the changes in Tregs in SFTS and predict the progression of SFTS.

Keywords::

• Severe fever with thrombocytopenia syndrome
• SFTS
• CD4 + CD25+ Foxp3 + cells
• CD4 + CD25 + cells

Acknowledgments

We would like to thank the teachers at the Center for Stem Cell Research and Application for technical assistance and the professors in the Department of Infection Disease for their help in collecting samples.

Declaration of interest: This work was supported by the National Nature Science Foundation of China (grant no. 81171638). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.