Ayala L Angel, Varady Erika S, Zhou Cuiwen, Chen Xiyu, Valdovinos Abigail, Ahmedani Alizeh H, Hisoire Gabriella L, Nguyen Pauline U, Scarfone Vanessa M, Inlay Matthew A
Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA, USA.
Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA.
Methods Mol Biol. 2025;2907:237-257. doi: 10.1007/978-1-0716-4430-0_11.
Acute graft-versus-host disease (aGVHD) remains a common life-threatening complication associated with allogeneic hematopoietic cell transplantation (allo-HCT) and is a major contributor to posttransplant mortality and morbidity. In allo-HCT, allogeneic T cells recognize host tissues as foreign and mount an immune response, causing inflammation and tissue damage. Traditionally, GVHD patients receive a regimen of immunosuppressive glucocorticoids after the onset of symptoms; however, many groups are developing prophylactic strategies due to the consequences associated with long-term glucocorticoid administration. Despite the advances made to mitigate GVHD, it remains a risk following allo-HCT; thus, new therapies are required to improve the safety of this therapy. Here, we use a prophylactic strategy that leverages graft manipulation as a way to induce tolerance upon transplantation. This chapter focuses on the techniques involved in conditioning donor cells, transplantation, and posttransplantation analysis of immune cells in a murine major histocompatibility complex (MHC) mismatched model of GVHD.
急性移植物抗宿主病（aGVHD）仍然是异基因造血细胞移植（allo-HCT）常见的危及生命的并发症，并且是移植后死亡率和发病率的主要促成因素。在allo-HCT中，异基因T细胞将宿主组织识别为外来物并引发免疫反应，导致炎症和组织损伤。传统上，GVHD患者在症状出现后接受免疫抑制性糖皮质激素治疗方案；然而，由于长期使用糖皮质激素带来的后果，许多研究团队正在开发预防策略。尽管在减轻GVHD方面取得了进展，但它在allo-HCT后仍然是一种风险；因此，需要新的疗法来提高这种治疗的安全性。在这里，我们使用一种预防策略，利用移植物操作作为移植时诱导免疫耐受的一种方法。本章重点介绍在小鼠主要组织相容性复合体（MHC）错配的GVHD模型中，对供体细胞进行预处理、移植以及移植后免疫细胞分析所涉及的技术。
