Nguyen Hung D, Huong Phung Thanh, Hossack Krystal, Gurshaney Sanjeev, Ezhakunnel Kevin, Huynh Thien-Huong, Alvarez Anamaria Morales, Le Nhat-Tu, Luu Hung N
Cancer Division, Burnett School of Biomedical Sciences, University of Central Florida;
Department of Biochemistry, Hanoi University of Pharmacy.
J Vis Exp. 2020 Mar 17(157). doi: 10.3791/60083.
Allogeneic bone marrow transplantation (BMT) is an effective therapy for hematological malignancies due to the graft-versus-leukemia (GVL) effect to eradicate tumors. However, its application is limited by the development of graft-versus-host disease (GVHD), a major complication of BMT. GVHD is evoked when T-cells in the donor grafts recognizealloantigen expressed by recipient cells and mount unwanted immunological attacks against recipient healthy tissues. Thus, traditional therapies are designed to suppress donor T-cell alloreactivity. However, these approaches substantially impair the GVL effect so that the recipient's survival is not improved. Understanding the effects of therapeutic approaches on BMT, GVL, and GVHD, is thus essential. Due to the antigen-presenting and cytokine-secreting capacities to stimulate donor T-cells, recipient dendritic cells (DCs) play a significant role in the induction of GVHD. Therefore, targeting recipient DCs becomes a potential approach for controlling GVHD. This work provides a description of a novel BMT platform to investigate how host DCs regulate GVH and GVL responses after transplantation. Also presented is an effective BMT model to study the biology of GVHD and GVL after transplantation.
异基因骨髓移植（BMT）是治疗血液系统恶性肿瘤的一种有效疗法，因其具有移植物抗白血病（GVL）效应可根除肿瘤。然而，其应用受到移植物抗宿主病（GVHD）的限制，GVHD是BMT的一种主要并发症。当供体移植物中的T细胞识别受体细胞表达的同种异体抗原并对受体健康组织发起不必要的免疫攻击时，就会引发GVHD。因此，传统疗法旨在抑制供体T细胞的同种异体反应性。然而，这些方法会严重损害GVL效应，从而无法提高受体的生存率。因此，了解治疗方法对BMT、GVL和GVHD的影响至关重要。由于受体树突状细胞（DC）具有抗原呈递和分泌细胞因子以刺激供体T细胞的能力，因此在GVHD的诱导中发挥着重要作用。因此，靶向受体DC成为控制GVHD的一种潜在方法。这项工作描述了一个新型的BMT平台，用于研究宿主DC在移植后如何调节GVH和GVL反应。还展示了一个有效的BMT模型，用于研究移植后GVHD和GVL的生物学特性。
