Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.
Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China.
Front Immunol. 2022 Feb 10;13:823352. doi: 10.3389/fimmu.2022.823352. eCollection 2022.
Heterogeneous T cells in acute myeloid leukemia (AML) have the combinatorial variety generated by different T cell receptors (TCRs). γδ T cells are a distinct subgroup of T cells containing TCRγ () and TCRδ () subfamilies with diverse structural and functional heterogeneity. Our previous study showed that clonally expanded T cells might benefit the immune response directed against AML. However, the features of the repertoire in AML remain unknown. To fully characterize the features of γδ T cells, we analyzed the distribution and clonality of subfamilies ( is also termed ), the proportions of γδ T cell subsets, and their effects on the overall survival (OS) of patients with AML.
In this study, the complementarity-determining region 3 (CDR3) size of subfamilies in γδ T cells of peripheral blood (PB) from AML patients were analyzed by Genescan analysis. Expression levels of subfamilies were performed by real-time quantitative PCR. The proportions of total γδ T cells and their Vγ9 Vδ2 T cells subsets were detected by multicolor flow cytometry assay. We further compared the correlation among the gene expression levels, the proportion of Vγ9 Vδ2 T cells, and OS in AML.
We first found that the distribution pattern and clonality of subfamilies were changed. The expression frequencies and gene expression levels of three subfamilies in AML samples were significantly lower than those in healthy individuals (HIs). Compared with HIs, the proportions of total γδ T cells and Vγ9 Vδ2 T cells were also significantly decreased in patients with AML. In addition, patients with AML who had higher expression levels of the gene and higher proportion of Vγ9 Vδ2 T cells showed better OS than their counterparts. Furthermore, high expression levels of and proportion of Vγ9 Vδ2 T cells were identified as independent protective factors for complete remission in patients with AML.
The restriction of usage might be related to the preference of usage of γδ T cells. Higher expression of subfamilies might be associated with better OS in AML. Higher expression and increased Vγ9 Vδ2 T cells subfamilies might indicate a better prognosis in patients with AML.
急性髓系白血病（AML）中的异质性 T 细胞具有由不同 T 细胞受体（TCR）产生的组合多样性。γδ T 细胞是 T 细胞的一个独特亚群，包含 TCRγ（）和 TCRδ（）亚家族，具有不同的结构和功能异质性。我们之前的研究表明，克隆扩增的 T 细胞可能有益于针对 AML 的免疫反应。然而，AML 中 γδ T 细胞受体库的特征尚不清楚。为了充分描述 γδ T 细胞的特征，我们分析了外周血（PB）中 γδ T 细胞的 亚家族（也称为 ）的分布和克隆性、γδ T 细胞亚群的比例及其对 AML 患者总生存（OS）的影响。
在这项研究中，通过基因扫描分析分析了 AML 患者外周血（PB）γδ T 细胞中 亚家族的互补决定区 3（CDR3）大小。通过实时定量 PCR 检测 亚家族的表达水平。通过多色流式细胞术检测总 γδ T 细胞及其 Vγ9 Vδ2 T 细胞亚群的比例。我们进一步比较了 AML 中 基因表达水平、Vγ9 Vδ2 T 细胞比例与 OS 之间的相关性。
我们首先发现 亚家族的分布模式和克隆性发生了变化。AML 样本中三种 亚家族的表达频率和基因表达水平均明显低于健康个体（HIs）。与 HIs 相比，AML 患者总 γδ T 细胞和 Vγ9 Vδ2 T 细胞的比例也明显降低。此外，AML 患者中 基因表达水平较高且 Vγ9 Vδ2 T 细胞比例较高的患者 OS 较好。此外，高 基因表达水平和 Vγ9 Vδ2 T 细胞亚群比例被确定为 AML 患者完全缓解的独立保护因素。
利用的限制可能与 γδ T 细胞利用的偏好有关。较高的 亚家族表达可能与 AML 中的 OS 相关。较高的 表达和增加的 Vγ9 Vδ2 T 细胞亚家族可能表明 AML 患者的预后较好。
