文章：

T细胞受体Vβ偏移在儿童难治性血细胞减少症中频繁发生，并与效应细胞毒性T细胞的扩增相关：EWOG-MDS的前瞻性研究

T-cell receptor Vβ skewing frequently occurs in refractory cytopenia of childhood and is associated with an expansion of effector cytotoxic T cells: a prospective study by EWOG-MDS

原文发布日期：2014-05-02

DOI: 10.1038/bcj.2014.28

类型: Original Article

开放获取: 是

英文摘要：

Immunosuppressive therapy (IST), consisting of antithymocyte globulin and cyclosporine A, is effective in refractory cytopenia of childhood (RCC), suggesting that, similar to low-grade myelodysplastic syndromes in adult patients, T lymphocytes are involved in suppressing hematopoiesis in a subset of RCC patients. However, the potential role of a T-cell-mediated pathophysiology in RCC remains poorly explored. In a cohort of 92 RCC patients, we prospectively assessed the frequency of T-cell receptor (TCR) β-chain variable (Vβ) domain skewing in bone marrow and peripheral blood by heteroduplex PCR, and analyzed T-cell subsets in peripheral blood by flow cytometry. TCRVβ skewing was present in 40% of RCC patients. TCRVβ skewing did not correlate with bone marrow cellularity, karyotype, transfusion history, HLA-DR15 or the presence of a PNH clone. In 28 patients treated with IST, TCRVβ skewing was not clearly related with treatment response. However, TCRVβ skewing did correlate with a disturbed CD4+/CD8+ T-cell ratio, a reduction in naive CD8+ T cells, an expansion of effector CD8+ T cells and an increase in activated CD8+ T cells (defined as HLA-DR+, CD57+ or CD56+). These data suggest that T lymphocytes contribute to RCC pathogenesis in a proportion of patients, and provide a rationale for treatment with IST in selected patients with RCC.

摘要翻译： 

免疫抑制疗法（IST）——包含抗胸腺细胞球蛋白与环孢素A——对儿童难治性血细胞减少症（RCC）具有疗效，这表明与成人低危骨髓增生异常综合征类似，部分RCC患者的T淋巴细胞参与抑制造血功能。然而，T细胞介导的病理生理机制在RCC中的潜在作用仍待深入探索。通过对92例RCC患者的前瞻性研究，我们采用异源双链PCR技术检测了骨髓及外周血中T细胞受体β链可变区偏移频率，并通过流式细胞术分析了外周血T细胞亚群。结果显示40%的RCC患者存在TCRVβ偏移现象，该现象与骨髓细胞密度、核型、输血史、HLA-DR15表达或PNH克隆无显著相关性。在28例接受IST治疗的患者中，TCRVβ偏移与治疗反应未见明确关联。但值得注意的是，TCRVβ偏移与CD4+/CD8+T细胞比例失衡、初始CD8+T细胞减少、效应CD8+T细胞扩增及活化CD8+T细胞（定义为HLA-DR+、CD57+或CD56+）增加存在相关性。这些数据表明T淋巴细胞在部分RCC患者的发病机制中发挥作用，为特定RCC患者群体采用IST治疗提供了理论依据。

原文链接：

T-cell receptor Vβ skewing frequently occurs in refractory cytopenia of childhood and is associated with an expansion of effector cytotoxic T cells: a prospective study by EWOG-MDS