Interleukin-17-producing CD4+ T lymphocytes are increased in patients with primary immune thrombocytopenia.

Abstract

The present study was performed to investigate the role of interleukin-17-producing CD4-positive T cells in the pathogenesis of primary immune thrombocytopenia (ITP). Peripheral blood was collected from ITP patients and healthy controls. The immunophenotyping of T lymphocytes and the detection of T helper 1/2/17 (Th1/Th2/Th17) cells were performed by flow cytometry, Th1/Th2/Th17-associated cytokines were determined by cytokines microarray and ELISA. The association between Th17 and T regulatory cells (Tregs) was also investigated. The percentage of Th17 and Th1 cells were markedly increased in ITP patients especially in those with severe ITP compared with normal controls. Th17 cytokines microarray revealed the upregulation of proinflammatory cytokines and downregulation of inflammatory inhibitory cytokines in ITP patients compared with that in the normal controls. Further ELISA analysis verified high levels of Th17-associated proinflammatory cytokines such as interleukin-17A/F, interleukin-6 and interleukin-23 and low levels of inflammatory inhibitory factors including interleukin-10 and transforming growth factor-β in ITP patients compared with normal controls. We also observed that the ratio of Th17/Treg was significantly higher in severe ITP than that in mild ITP and normal controls and inversely correlated with platelet count. In addition, Tregs from ITP patients could suppress the secretion of interferon-γ by effector CD4-positive T cells, but had no effect on interleukin-17 production in vitro. Th17 cells are increased in ITP patients, and the inversion of Th17/Treg may contribute to the activation of autoimmunity.