Allogeneic immune cells, particularly T cells in donor grafts, recognize and eliminate leukemic cells via graft-versus-leukemia (GVL) reactivity, and transfer of these cells is often used for high-risk hematological malignancies, including acute myeloid leukemia. Unfortunately, these cells also attack host normal tissues through the often fatal graft-versus-host disease (GVHD). Full separation of GVL activity from GVHD has yet to be achieved. Here, we show that, in mice and humans, a population of interleukin-9 (IL-9)–producing T cells activated via the ST2–IL-33 pathway (T9_IL-33 cells) increases GVL while decreasing GVHD through two opposing mechanisms: protection from fatal immunity by amphiregulin expression and augmentation of antileukemic activity compared with T9, T1, and unmanipulated T cells through CD8α expression. Thus, adoptive transfer of allogeneic T9_IL-33 cells offers an attractive approach for separating GVL activity from GVHD.

同种异体免疫细胞，特别是供体移植物中的 T 细胞，通过移植物抗白血病 (GVL) 反应性识别并消除白血病细胞，这些细胞的转移通常用于治疗高危血液恶性肿瘤，包括急性髓系白血病。不幸的是，这些细胞还通过通常致命的移植物抗宿主病（GVHD）攻击宿主正常组织。 GVL 活性与 GVHD 的完全分离尚未实现。在这里，我们发现，在小鼠和人类中，通过 ST2–IL-33 途径激活的产生白细胞介素 9 (IL-9) 的 T 细胞群（T9 _IL-33细胞）通过两种相反的方式增加 GVL，同时降低 GVHD。机制：通过双调蛋白表达保护免受致命性免疫，并通过 CD8α 表达与 T9、T1 和未操作的 T 细胞相比增强抗白血病活性。因此，同种异体 T9 _IL-33细胞的过继转移为分离 GVL 活性与 GVHD 提供了一种有吸引力的方法。