Department of Physiology, Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
Research Laboratory, Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
J Interferon Cytokine Res. 2021 Sep;41(9):310-318. doi: 10.1089/jir.2021.0032.
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 injection of C57BL/6 (H-2) spleen cells into irradiated BDF1 (H-2) mice, the hosts developed interferon-gamma (IFN-γ)-dependent bone marrow (BM) GVHD on days 5-17. When transgenic H-2 lymphoma cells were inoculated into irradiated, H-2 splenocyte-transplanted H-2 mice, the infiltration of macrophages cytotoxic against transgenic H-2 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 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.
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存在争议，尚未确定移植物对宿主的特定细胞毒性活性。在将 C57BL/6（H-2）脾细胞注射到辐照的 BDF1（H-2）小鼠后，宿主在第 5-17 天出现干扰素-γ（IFN-γ）依赖性骨髓（BM）GVHD。当转基因 H-2 淋巴瘤细胞接种到辐照的、H-2 脾细胞移植的 H-2 小鼠中时，对转基因 H-2 小鼠皮肤上皮具有细胞毒性的巨噬细胞浸润到腹腔中，先于依赖白细胞介素（IL）-2 的细胞毒性 T 淋巴细胞（CTL）浸润数天，以实现移植物抗白血病（GVL）效应。相比之下，单独将同种异体 BM 移植到辐照的小鼠中不会在 44 天内引起 GVHD，而分别注射移植物抗宿主巨噬细胞或移植物抗宿主 CTL 以及同种异体 BM 会在没有 GVHD 的情况下引起 GVHD 或促进 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 Th1（IFN-γ/IL-2）反应的一组反应，并且 BM 移植后移植物 T 细胞的激活而不是抑制跳过了 GVHD。
