Yue Keli, Liang Shuang, Wu Ning, Jia Mingzhu, Gao Haitao, Cheng Cong, Hu Lijuan, Liu Jiangying
Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
Eur J Immunol. 2025 Aug;55(8):e70025. doi: 10.1002/eji.70025.
In addition to exhibiting significant cytotoxic capabilities, γδ T cells play a crucial role as a bridge between innate and adaptive immunity. Although γδ T cells have been demonstrated to orchestrate interactions with other immune cells, their impact on αβ T cells in the setting of acute myeloid leukemia (AML) remains unexplored. In this study, we found that functional deficiencies of αβ T cells were significantly associated with the downregulation of HLA-DR γδ T cells in patients newly diagnosed with AML. Vδ2 T cells, which constitute a predominant subset of γδ T cells in human peripheral blood, exhibited elevated levels of HLA-DR following ex vivo expansion. Notably, a lower dose of the expanded Vδ2 T cells did not induce direct cytotoxicity against AML cells; instead, they significantly enhanced the cytotoxic capacity of primary αβ T cells toward AML cells. Furthermore, blockade of HLA-DR on Vδ2 T cells markedly diminished this facilitating effect. Taken together, our findings demonstrate an important indirect role for Vδ2 T cells beyond their direct killing ability in the context of anti-AML immunity and provide novel insights into the therapeutic potential of adoptive Vδ2 T cell therapy.
除了具有显著的细胞毒性能力外，γδ T细胞作为先天性免疫和适应性免疫之间的桥梁发挥着关键作用。尽管γδ T细胞已被证明能协调与其他免疫细胞的相互作用，但它们在急性髓系白血病（AML）背景下对αβ T细胞的影响仍未得到探索。在本研究中，我们发现新诊断的AML患者中，αβ T细胞的功能缺陷与HLA-DR γδ T细胞的下调显著相关。Vδ2 T细胞是人类外周血中γδ T细胞的主要亚群，在体外扩增后HLA-DR水平升高。值得注意的是，较低剂量的扩增Vδ2 T细胞不会诱导对AML细胞的直接细胞毒性；相反，它们显著增强了原代αβ T细胞对AML细胞的细胞毒性能力。此外，阻断Vδ2 T细胞上的HLA-DR可显著减弱这种促进作用。综上所述，我们的研究结果证明了Vδ2 T细胞在抗AML免疫背景下除直接杀伤能力之外的重要间接作用，并为过继性Vδ2 T细胞治疗的治疗潜力提供了新的见解。
