Figure 5. Correlations of Tc17 with CD8 and CD8;CD4 in ITP. Positive correlation of Tc17 with CD8:CD4 ratio (r = 0.6256, P = 0.001) and positive correlation of Tc17 with percentage of CD8+ T cells (r = 0.5562, P = 0.006) in ITP. doi:10.1371/journal.pone.0026522.g005 percentage of Tc17 in ITP patients was decreased with the addition of DEX in vitro, strongly suggesting that Tc17 may be involved in the pathogenesis of ITP. Also, the number of Th17 cells was increased in newly-diagnosed ITP patients compared with healthy controls; similar results were produced in our previous research [9]. In the current study we confirmed the increased number of Th17 cells in ITP patients. Moreover, due to the similar trends in increased numbers of Th17 cells and Tc17 in ITP patients, we compared the ratio of Th17:Tc17 between newly-diagnosed patients, ITP patients with complete response, and healthy controls, and showed that the Th17:Tc17 ratio was decreased in newly-diagnosed patients compared with healthy controls and patients who had CR. This indicated that Tc17 were increased more predominately than Th17 in patients with active ITP. Thus, we presume that the Tc17 subset might play a more important role in the immunopathology of ITP patients. In addition, the Tc17 differentiate along a developmental program that is similar to the one described for Th17 cells [23],[24],[25]. The positive correlation of the percentages between Th17 cells and Tc17 in control samples suggests that Tc17 is co- regulated with Th17 cells during differentiation in normal human peripheral blood, and substantially advanced our understanding of T-cell mediated immunity. Th17 cells and Tc17 may play a cooperative or synergistic function under conditions of T cell- mediated immunity; however, no significant correlation existed between Tc17 and Th17 cells in the peripheral blood of ITP Tc17 in ITP Figure 6. The response of Tc17 and Th17 cells to DEX in ITP patients. The percentages of Tc17 and Th17 cells had a decreasing tendency with the increase in DEX concentration in culture media. doi:10.1371/journal.pone.0026522.g006 patients. These results strongly support the hypothesis that there is a pathologic differentiation of T cell subsets in patients with ITP, which ultimately causes a derangement between Tc17 and Th17 cells. The CD4:CD8 ratio is an important index in immune-related diseases [26]. A low CD4:CD8 ratio may be a sign of immune dysfunction [27]. Interestingly, in the current study we showed that the CD4:CD8 ratio and percentage of CD8 cells were elevated in patients with ITP compared with healthy controls. Also, Tc17 was positively correlated with the percentage of CD8+ cells and the CD8:CD4 ratio. The results in the control group were dissimilar. The mechanism underlying the correlation between Tc17 and the CD4:CD8 ratio or the percentage of CD8 cells should be clarified in future studies. Platelet-reactive antibodies are not detected in all patients with ITP. A subset of patients do not respond to pharmacologic therapy, antibody-mediated platelet clearance, or B-cell suppres- sion, suggesting the possible involvement of other pathogenic mechanisms, such as Ag shedding, and T cell-mediated platelet destruction or marrow suppression [4]. We detected Tc17 and specific anti-platelet GPIIb/IIIa and/or GPIb/IX autoantibodies in 23 patients by MAIPA. The results showed that the number of Tc17 and titers of autoantibodies had a marginal negative correlation, suggesting cellular and humoral immunity might be complementary in the pathogenesis of ITP. Taken together, our study demonstrated that the predominant Tc17 might differentiate and develop under the influence of a particular microenvironment and eventually cause an imbalance in Tc17 and Th17 cell subsets in patients with ITP. The Tc17 subset could be decreased with effective clinical treatment. T-cell function derangement has been demonstrated in patients with ITP with abnormal T cells secreting IL-17. The elevated Tc17 may play a potential role in the development and progression of ITP, and blocking the abnormally increased number of Tc17 cells may lead to a novel therapeutic strategy for ITP. Author Contributions Conceived and designed the experiments: DXM. Performed the experiments: YH YYZ. Analyzed the data: SY LZ NNS. Contributed reagents/materials/analysis tools: MH CYJ. Wrote the paper: YH XGL. PLoS ONE | www.plosone.org 6 October 2011 | Volume 6 | Issue 10 | e26522