Recovery of Natural Interferon-α/β-producing Cells after Allogeneic Hematopoietic Stem Cell Transplantation

异体造血干细胞移植后天然干扰素-α/β产生细胞的恢复

• 批准号: 13671062
• 负责人: KADOWAKI Norimitsu
• 金额: $ 2.3万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671062/
• 关键词: Allogeneic hematopoietic stem cell transplantation; Immune reconstitution; Innate immunity; Dendritic cells; Type I interferon; graft versus host disease; Glucocorticoid; インターフェロン; 自然免疫系; 免疫不全; 日和見感染症; 移植片対宿主病(GVHD); ステロイド

Delayed recovery of the immune system is a major cause of post-transplant infection. Natural interferon (IFN)-α/β-producing cells (IPC) appear to play a critical role in inducing effective immune responses to a variety of microbial pathogens by producing an enormous amount of IFN-α/β and thereafter by differentiating into dendritic cells. Here, we examined the recovery of IPC as well as other immune cells in 28 patients after allogeneic hematopoietic stem cell transplantation (HSCT) in order to investigate the role of IPC in post-transplant immune reconstitution. In uncomplicated cases, IPC frequency recovered to the lower range of normal values within 30 days after transplantation, resembling the prompt recovery of other cell types in innate immunity. In contrast, the recovery of IPC was profoundly suppressed in the cases with acute GVHD and glucocorticoid administration. The patients with lower numbers of IPC were significantly more susceptible to viral infection. The prompt recovery of IPC in uncomplicated cases may contribute to establishing a first line of host defense at the early stage after allogeneic HSCT, whereas the marked suppression of IPC recovery accompanying acute GVHD and glucocorticoid administration may increase the risk of opportunistic infections.

免疫系统的延迟恢复是移植后感染的主要原因。天然干扰素（IFN）-α/β产生细胞（IPC）通过产生大量IFN-α/β并随后分化为树突状细胞而在诱导针对多种微生物病原体的有效免疫应答中发挥关键作用。在这里，我们检查了IPC的恢复以及其他免疫细胞在28例异基因造血干细胞移植（HSCT）后，以探讨IPC在移植后免疫重建的作用。在不复杂的情况下，IPC频率恢复到正常值的较低范围内移植后30天内，类似于其他细胞类型的先天免疫的迅速恢复。相反，IPC的恢复在急性GVHD和糖皮质激素给药的情况下被深度抑制。IPC数量较少的患者更容易感染病毒。在无并发症的情况下，IPC的迅速恢复可能有助于在异基因HSCT后的早期阶段建立宿主防御的第一道防线，而伴随急性GVHD和糖皮质激素给药的IPC恢复的显著抑制可能增加机会性感染的风险。

项目成果

Toshio Kitawaki, et al.: "Compromised Recovery of Natural Interferon-α/β-producing Cells after Allogeneic Hematopoietic Stem Cell Transplantation Complicated by Acute Graft versus Host Disease and Glucocorticoid Administration"Bone Marrow Transplantation.

Toshio Kitawaki等人：“同种异体造血干细胞移植后天然干扰素-α/β产生细胞的恢复受损，并发急性移植物抗宿主病和糖皮质激素给药”骨髓移植。

Toshio Kitawaki, Norimitsu Kadowaki, Takayuki Ishikawa, Tatsuo Ichinohe, and Takashi Uchiyama: "Compromised recovery of natural interferon-α/β-producing cells after allogeneic hematopoietic stem cell tratlsplantation complicated by acute graft versus host

Toshio Kitawaki、Norimitsu Kadowaki、Takayuki Ishikawa、Tatsuo Ichinohe 和 Takashi Uchiyama：“同种异体造血干细胞移植后并发急性移植物抗宿主反应，天然干扰素 α/β 产生细胞的恢复受损