The Mechanism Of Abnormal T Cells Subsets Involved Immune Thrombocytopenia

Immune thrombocytopenia (ITP) is a kind of platelet immunological failure featuresof autoimmune disease. Clinically, ITP is divided into acute and chronic ITP. Chronic ITPdisease is mainly in20-50years old adult people. Female incidence rate is2-3times morethan that of male. Most chronic ITP patients lack clinical symptoms and definite reasons.Acute ITP is mainly occurred in children about2-5years old after virous infection andvaccination and there is no gender difference. The general course of acute ITP is four to sixweeks and the majority of children with the disease can relieve itself, rarely relapse afterrecovery. Acute ITP usually happens in spring/winter and the fastigium of virous infection.According to clinical experience, acute ITP is mostly spontaneous remission. However thecause of chronic ITP is complex. More and more evidence shows that, other than humoralimmune function disorders, imbalance of Th1/Th2is happened in ITP patients and Th1type reaction is dominant. In addition, it is reported that the number of Treg and Th17cellswere abnormal in ITP patients.Recent progress of ITP treatment enables us to use three distinct approaches toincrease platelet mass:(1) by suppression of platelet clearance, e.g. splenectomy,(2) bysuppression or modification of abnormal immune responses, e.g. corticosteroids orrituximab, and (3) by stimulation of platelet production, e.g. TPO-RAs. But for somepatients with chronic ITP, the treatment effect is not significant.There are reports of short-range high concentrations of dexamethasone has a goodtherapeutic effect for patients with chronic ITP, but the mechanism is unknown. Thisresearch attempts to study the therapeutic effect of dexamethasone in patients with ITP andto elucidate its mechanism of action. In this paper, we first analyzed the T cell subsets in the peripheral blood of ITP patients using FCM including Th1, Th2, Treg and Th17cells.Meanwhile, IL2, IFN-gama, IL4, IL10, TGFbeta and IL17cytokines were assessed byELISA; mRNA of T-bet, GATA-3, Foxp3and ROR γ t were checked using real timefluorescent quantitative PCR. Furthermore, we evaluated the therapeutic effect of shortcourse-high concentration of dexamethasone in the treatment of patients with chronic ITPand studied the mechanism of dexamethasone in treatment of ITP.We analyzed30normal people and30ITP patients. Our results showed that thecontent of Th1cells did not change significantly in normal subjects and in patients withITP, and the content of Th2cells in patients with ITP was significantly lower. At the sametime, we analyzed another two T cells subsets Treg and Th17. The results showed that thenumber of Treg cells was reduced and Th17cells increased in patients with ITP. ELISAresults showd that Th1type cytokines (IL2and IFN-gama) were increased in the peripheralblood of patients with ITP, and Th2type cytokines (IL4and IL10) was significantlydown-regulated.As the change of Treg cells and Th17cells, TGFbeta and IL17were also decreasedand increased respectively in the peripheral blood of patients with ITP. Realtime PCRresults showed there were no significant changes of the expression of T-bet in peripheralblood of patients with ITP, but the expression of GATA-3and Foxp3were significantlylower in patients with ITP, and the expression of ROR γ t is higher than normal people.Subsequently, we treated10ITP patients with high concentration of dexamethasone. Thetreatment results showed that70%of the patients after treatment significantly increased thenumber of platelets. At the same time, T cell subsets and transcription factors wereanalyzed. The results show that, Th2cells and Treg cells in peripheral blood of patientstreated with dexamethasone compared to untreated group significantly increased, and Th17cells were significantly decreased. At the same time, we found that expression oftranscription factor is changed as T cells subsets. In order to further reveal the mechanismof dexamethasone in changing the T cell subsets in ITP, we isolated the T cells from normal people and treated with dexamethasone. The results show that dexamethasone caninhibit the expression of ROR γ T, but promotes the expression of GATA-3andFoxp3.These results suggest that dexamethasone can correct the T cell subsets in patientswith ITP by regulating the expression level of transcription factors.In summary, we for thefirst time analyzed the content of T cells subsets, cytokines and transcription factors in ITPpatients, providing more evidence for abnormal T cell subsets in the pathogenesis of ITP.Mechanism and treatment of patients with ITP to the high concentration of dexamethasoneare discussed. These results provide important information for understanding thepathogenesis and treatment of ITP.