Alteration in frequency and function of CD4⁺CD25⁺FOXP3⁺ regulatory T cells in patients with immune thrombocytopenic purpura.
Alteration in frequency and function of CD4⁺CD25⁺FOXP3⁺ regulatory T cells in patients with immune thrombocytopenic purpura.
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发表时间：
2014-03
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通讯作者：
N. Arandi;A. Mirshafiey;M. Jeddi-Tehrani;M. Shaghaghi;B. Sadeghi;Hassan Abolhassani;R. Sharifian;M. Rahiminejad;A. Aghamohammadi
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作者：
N. Arandi;A. Mirshafiey;M. Jeddi-Tehrani;M. Shaghaghi;B. Sadeghi;Hassan Abolhassani;R. Sharifian;M. Rahiminejad;A. Aghamohammadi
免疫性血小板减少性紫癜（ITP）是一种自身免疫性出血性疾病，其特征是产生抗血小板抗原的自身抗体。为了研究调节性T细胞（Regulatory T cells，TCRs）在ITP患者和健康对照中的分布和功能，我们收集了20例ITP患者和20例年龄和性别相匹配的健康对照。分离外周血单个核细胞，流式细胞术测定TCFs的比例。实时荧光定量PCR TaqMan法检测细胞毒性T淋巴细胞相关抗原4（CTLA-4）和糖皮质激素诱导的肿瘤坏死因子受体（GITR）的表达。结果显示，ITP患者外周血中Tcl 3的表达频率和FOXP 3蛋白的平均荧光强度均较健康对照组显著降低，而Tcl 3的表达频率和FOXP 3蛋白的平均荧光强度均较健康对照组显著降低。此外，ITP患者CTLA-4和GITR mRNA的相对表达量均显著降低（分别为P=0.02和P=0.006）。与对照组相比，ITP患者中TdR的抑制功能也减弱。ITP患者IL-10和TGF-β细胞因子的产生量均低于对照组，提示Treg频率和功能特征的改变可能是导致ITP患者自身耐受丧失和随后的破坏性免疫反应的原因。
Immune thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder characterized by production of auto-antibodies against platelet antigens. It is obvious that regulatory T cells (Tregs) have a major role in controlling immune homeostasis and preventing autoimmunity.To investigate the frequency and functions of Tregs, twenty ITP patients and twenty age- and sex-matched healthy controls were recruited. The peripheral blood mononuclear cells were isolated and the proportion of Tregs was defined by flow cytometry method. The expression of immune-regulatory markers, cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and glucocorticoid induced tumor necrosis factor receptor (GITR) were also assessed by quantitative Real-time PCR TaqMan method. For evaluation of Treg function, Tregs were enriched and their ability to inhibit proliferation of T cells was measured and levels of immune-regulatory cytokines IL-10 and TGF-β were also measured.Results showed that the frequency of Tregs and the mean fluorescence intensity of FOXP3 protein significantly decreased in ITP patients compared to those in healthy controls. In addition, there was a significant reduction in relative expression of both CTLA-4 and GITR mRNA in ITP patients (P=0.02 and P=0.006, respectively). The suppressive function of Tregs also diminished in ITP patients compared to that in controls. Both IL-10 and TGF-β cytokines were produced in lower amounts in ITP patients than controls.It could be concluded that alteration in Treg frequency and functional characteristics might be responsible for loss of self-tolerance and subsequently destructive immune responses observed in ITP patients.