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

Year: 2025

Type: article

Abstract: 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.

Source: European Journal of Immunology

DOI: 10.1002/eji.70025