Department of Hematology, Zhongshan Hospital Fudan University, Shanghai, 200032, China.
Department of Hematology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China.
Ann Hematol. 2019 Aug;98(8):1845-1854. doi: 10.1007/s00277-019-03716-9. Epub 2019 Jun 1.
Primary immune thrombocytopenia is an autoimmune disease, characterized with decreased platelet and increased risk of bleeding. Recent studies have shown the reduction and dysfunction of regulatory T (Treg) cells in ITP patients. CD39 is highly expressed on the surface of Treg cells. It degrades ATP to AMP and CD73 dephosphorylates AMP into adenosine. Then adenosine binds with adenosine receptor and suppresses immune response by activating Treg cells and inhibiting the release of inflammatory cytokines from effector T (Teff) cells. Adenosine receptor has several subtypes and adenosine A2A receptor (A2AR) plays a crucial role especially within lymphocytes. The CD39 Treg cells and the expression of A2AR showed abnormality in some autoimmune disease. But knowledge of CD39 Treg cells and A2AR which are crucial in the adenosine immunosuppressive pathway is still limited in ITP. Thirty-one adult patients with newly diagnosed ITP were enrolled in this study. CD39 and A2AR expression was measured by flow cytometry and RT-PCR. The function of CD39 was reflected by the change of ATP concentration detected by CellTiter-Glo Luminescent Cell Viability Assay. CD39 expression within CD4CD25 Treg cells in ITP patients was decreased compared to normal controls. After high-dose dexamethasone therapy, response (R) group showed increased CD39 expression within Treg cells while non-response (NR) group did not show any difference in contrast to those before treatment. The expression of A2AR in CD4CD25 Teff and CD4CD25 Treg cells was both lower in ITP patients than that of normal controls. After therapy, CD4CD25 Teff cells had higher A2AR expression while CD4CD25 Treg cells did not show any difference in comparison to that before treatment. The enzymatic activity of CD39 was damaged in ITP patients and improved after high-dose dexamethasone therapy. In ITP, there was not only numerical decrease but also impaired enzymatic activity in CD39 Treg cells. After high-dose dexamethasone treatment, these two defects could be reversed. Our results also suggested that ITP patients had reduced A2AR expression in both CD4CD25 Treg cells and CD4CD25 Teff cells. CD4CD25 Teff cells had increased A2AR expression after treatment.
原发性免疫性血小板减少症是一种自身免疫性疾病，其特征是血小板减少和出血风险增加。最近的研究表明，ITP 患者的调节性 T（Treg）细胞数量减少和功能障碍。CD39 在 Treg 细胞表面高度表达。它将 ATP 降解为 AMP，CD73 将 AMP 去磷酸化为腺苷。然后，腺苷与腺苷受体结合，通过激活 Treg 细胞和抑制效应 T（Teff）细胞释放炎症细胞因子来抑制免疫反应。腺苷受体有几个亚型，其中腺苷 A2A 受体（A2AR）在淋巴细胞中起着至关重要的作用。在一些自身免疫性疾病中，CD39 Treg 细胞和 A2AR 的表达出现异常。但是，在 ITP 中，对腺苷免疫抑制途径中至关重要的 CD39 Treg 细胞和 A2AR 的了解仍然有限。本研究纳入了 31 例新诊断为 ITP 的成年患者。通过流式细胞术和 RT-PCR 测量 CD39 和 A2AR 的表达。通过 CellTiter-Glo 发光细胞活力测定检测 ATP 浓度的变化来反映 CD39 的功能。与正常对照相比，ITP 患者 CD4CD25 Treg 细胞内的 CD39 表达降低。在大剂量地塞米松治疗后，反应（R）组 Treg 细胞内的 CD39 表达增加，而非反应（NR）组与治疗前相比没有任何差异。ITP 患者的 CD4CD25 Teff 和 CD4CD25 Treg 细胞中的 A2AR 表达均低于正常对照组。治疗后，CD4CD25 Teff 细胞中的 A2AR 表达升高，而 CD4CD25 Treg 细胞与治疗前相比没有差异。ITP 患者的 CD39 酶活性受损，大剂量地塞米松治疗后有所改善。在 ITP 中，CD39 Treg 细胞不仅数量减少，而且酶活性受损。在大剂量地塞米松治疗后，这两种缺陷可以得到逆转。我们的结果还表明，ITP 患者的 CD4CD25 Treg 细胞和 CD4CD25 Teff 细胞中 A2AR 表达均降低。治疗后，CD4CD25 Teff 细胞中的 A2AR 表达增加。
