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

IF 3.7 3区 医学 Q2 IMMUNOLOGY
Keli Yue, Shuang Liang, Ning Wu, Mingzhu Jia, Haitao Gao, Cong Cheng, Lijuan Hu, Jiangying Liu
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Abstract

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.

表达hla - dr的γδ T细胞促进αβ T细胞抗白血病活性
除了表现出显著的细胞毒性外,γδ T细胞作为先天免疫和适应性免疫之间的桥梁起着至关重要的作用。虽然γδ T细胞已被证明可以协调与其他免疫细胞的相互作用,但它们在急性髓性白血病(AML)中对αβ T细胞的影响尚不清楚。本研究发现,在新诊断的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细胞的细胞毒能力。此外,阻断HLA-DR对Vδ2+ T细胞的促进作用显著减弱。综上所述,我们的研究结果表明,在抗aml免疫的背景下,Vδ2+ T细胞除了具有直接杀伤能力外,还具有重要的间接作用,并为过继性Vδ2+ T细胞治疗的治疗潜力提供了新的见解。
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来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
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