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Transplantation of Graft Anti-Host Cytotoxic T Lymphocytes Along with Allogeneic Bone Marrow Skips Macrophage-Induced Graft-Versus-Host Disease
Journal of Interferon & Cytokine Research ( IF 1.9 ) Pub Date : 2021-09-17 , DOI: 10.1089/jir.2021.0032
Ryotaro Yoshida 1, 2 , Hidenori Yamana 1, 3 , Michihiro Hayashi 3 , Emi Yasuda 4 , Yuro Shibayama 4 , Yoshinobu Hirose 4 , Nobuhiko Tanigawa 3 , Kazuhisa Uchiyama 3 , Takahiro Kubota 1
Affiliation  

Graft-versus-host disease (GVHD) is a physiological response of the graft to allogeneic hosts. However, the effector cells, affected organ(s), and cytokines in the GVHD remain controversially discussed, without having determined a particular cytotoxic activity of the graft against the host. After i.v. injection of C57BL/6 (H-2b) spleen cells into irradiated BDF1 (H-2b/d) mice, the hosts developed interferon-gamma (IFN-γ)-dependent bone marrow (BM) GVHD on days 5–17. When H-2DdKd transgenic H-2b lymphoma cells were i.p. inoculated into irradiated, H-2b splenocyte-transplanted H-2b/d mice, the infiltration of macrophages cytotoxic against H-2DdKd transgenic H-2b mouse skin epithelia (a GVHD activity) into the peritoneal cavity preceded several days the infiltration of interleukin (IL)-2-dependent cytotoxic T lymphocytes (CTLs) to achieve a graft-versus-leukemia (GVL) effect. In contrast, allogeneic BM transplanted alone into the irradiated mice did not induce GVHD for 44 days, whereas i.v. injection of graft anti-host macrophages or graft anti-host CTLs along with allogeneic BM, respectively, induced GVHD or promoted the GVL effect in the absence of GVHD. These results revealed that macrophage-induced GVHD and the CTL-mediated GVL effect were a set (Th1: IFN-γ/IL-2) response of the graft to allogeneic hosts and leukemia cells, respectively, and that graft T cell activation rather than inhibition skipped GVHD after BM transplantation.

中文翻译:

移植抗宿主细胞毒性 T 淋巴细胞与同种异体骨髓的移植跳过巨噬细胞诱导的移植物抗宿主病

移植物抗宿主病 (GVHD) 是移植物对同种异体宿主的生理反应。然而,GVHD 中的效应细胞、受影响的器官和细胞因子仍然存在争议,但尚未确定移植物对宿主的特定细胞毒活性。将C57BL/6 (H-2 b ) 脾细胞静脉注射到受辐射的 BDF1 (H-2 b/d ) 小鼠后,宿主在第 5 天出现干扰素-γ (IFN-γ) 依赖性骨髓 (BM) GVHD –17。将H-2D d K d转基因 H-2 b淋巴瘤细胞ip接种到照射过的 H-2 b脾细胞移植 H-2 b/d小鼠,对H-2D d K d转基因 H-2 b小鼠皮肤上皮细胞(一种 GVHD 活性)具有细胞毒性的巨噬细胞浸润到腹膜腔中,在白细胞介素 (IL)-2 依赖性细胞毒性 T 淋巴细胞 (CTL) 浸润之前几天) 以实现移植物抗白血病 (GVL) 效果。相比之下,单独移植到受辐射小鼠体内的同种异体 BM 在 44 天内没有诱导 GVHD,而iv注射移植物抗宿主巨噬细胞或移植物抗宿主 CTLs 以及同种异体 BM 分别诱导 GVHD 或在没有 GVHD 的情况下促进 GVL 效应。这些结果表明,巨噬细胞诱导的 GVHD 和 CTL 介导的 GVL 效应分别是移植物对同种异体宿主和白血病细胞的一组 (Th1: IFN-γ/IL-2) 反应,并且移植物 T 细胞激活而不是BM移植后抑制跳过GVHD。
更新日期:2021-09-21
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