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表达 HLA-DR 的γδ T 细胞促进αβ T 细胞的抗白血病活性

英文原题:HLA-DR-Expressing γδ T Cells Facilitate the Anti-Leukemia Activity of αβ T Cells.

查看英文原题

HLA-DR-Expressing γδ T Cells Facilitate the Anti-Leukemia Activity of αβ T Cells.

PubMed 2025/08/01(内容时间) Eur J Immunol Q2 · IF 4.1(JCR 2025)

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中文摘要

除了具有显著的细胞毒性能力外,γδ T 细胞还作为连接固有免疫和适应性免疫的桥梁发挥关键作用。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,但其在急性髓系白血病(AML)背景下对 αβ T 细胞的影响仍未被探索。

在本研究中,我们发现 αβ T 细胞的功能缺陷与新诊断 AML 患者中 HLA-DR + γδ T 细胞的下调显著相关。Vδ2 + T 细胞是人外周血中 γδ T 细胞的主要亚群,在体外扩增后表现出 HLA-DR 水平升高。

值得注意的是,较低剂量的扩增 Vδ2 + T 细胞并未对 AML 细胞产生直接细胞毒性;相反,它们显著增强了原发性 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 明显削弱了这种促进作用。综上所述,我们的研究结果表明,Vδ2 + T 细胞在抗 AML 免疫中除了直接杀伤能力外还具有重要的间接作用,并为过继性 Vδ2 + T 细胞治疗的潜力提供了新的见解。

展开英文摘要原文

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.

论文信息

作者
Yue K、Liang S、Wu N、Jia M、Gao H、Cheng C、Hu L、Liu J
单位
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.China
期刊
European journal of immunology2025 Aug
原文标识
PubMed 40776532 · DOI 10.1002/eji.70025