Insufficient secretion of IL-10 by Tregs compromised its control on over-activated CD4+ T effector cells in newly diagnosed adult immune thrombocytopenia patients.

Feng Li, Lili Ji, Weiguang Wang, Fanli Hua, Yanxia Zhan, Shanhua Zou, Ling Yuan, Yang Ke, Zhihui Min, Dongli Song, Lihua Sun, Hao Chen, Yunfeng Cheng

Index: Immunol. Res. 61(3) , 269-80, (2015)

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Abstract

Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder. Excessive activated CD4(+) T effector cells (Teffs) and compromised regulatory T cells (Tregs) were reported in ITP patients, yet little is known about the mechanisms. Interleukin-10 (IL-10) is an important regulatory cytokine of Tregs in inflammatory condition. It has been recently highlighted that IL-10-producing Tregs contribute to the effective controls of several autoimmune diseases. Hence this study was aimed to examine the role of IL-10 produced by Tregs in newly diagnosed ITP patients. Newly diagnosed ITP patients and healthy volunteers were enrolled to assess the numbers of peripheral Th1, Th17 cells and Tregs. CD4(+)CD25(-)Teffs and CD4(+)CD25(+)Tregs were purified. CD4(+)CD25(-)Teffs, labeled with CFSE, were cultured alone or with Tregs for 5 days, and the supernatants were then collected for IL-10 concentration test. The role of IL-10 in Tregs' inhibitory function was also determined. In ITP patients, Teffs were excessively activated, while the Tregs were numerically and functionally impaired. The percentages of IL-10(+) Tregs in Tregs' population were found elevated dramatically in ITP patients but decreased in the remitted patients. The IL-10 concentrations in the cultured supernatant were decreased in ITP patients but elevated in the remitted patients. Furthermore, the IL-10 secretion by Tregs was dramatically decreased in ITP patients. IL-10 treatment enhanced the suppression effect of Tregs toward Teffs, whereas anti-IL-10 treatment boosted the proliferation of Teffs and Th17 cells. Excessive activated Teffs and impaired Tregs play major roles in the exuberant CD4(+) T cells immune responses of ITP. The inhibitory effect of Tregs toward Teffs is largely exerted by IL-10. Insufficient secretion of IL-10 compromises the inhibitory capability of Tregs against Teffs in newly diagnosed ITP patients.