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首页> 美国卫生研究院文献>Blood Cancer Journal >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
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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

机译：T细胞受体Vβ倾斜经常发生在儿童难治性血细胞减少症中并且与效应细胞毒性T细胞的扩增有关：EWOG-MDS的一项前瞻性研究

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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.
机译：免疫抑制疗法（IST）由抗胸腺细胞球蛋白和环孢霉素A组成，可有效治疗儿童难治性血细胞减少症（RCC），这表明，与成年患者的低度骨髓增生异常综合征相似，T淋巴细胞可抑制部分亚型的造血作用RCC患者。然而，在RCC中T细胞介导的病理生理学的潜在作用仍然很少被探索。在92名RCC患者中，我们前瞻性地通过异源双链PCR评估了骨髓和外周血中T细胞受体（TCR）β链可变（Vβ）结构域的偏斜频率，并通过分析了外周血中T细胞亚群流式细胞仪。 TCRVβ偏斜存在于40％的RCC患者中。 TCRVβ的倾斜与骨髓细胞，核型，输血史，HLA-DR15或PNH克隆的存在无关。在接受IST治疗的28例患者中，TCRVβ的偏斜与治疗反应没有明显关系。然而，TCRVβ的倾斜与CD4 + / CD8 + T细胞比率紊乱相关，即幼稚的CD8 + T细胞减少。 CD8 + T细胞的扩增和激活的CD8 + T细胞（定义为HLA-DR + ，CD57 + 或CD56 + ）。这些数据表明，T淋巴细胞在一定比例的患者中促成RCC发病机理，并为某些RCC患者选择IST治疗提供了依据。

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