Innate Immune Determinants of Graft-Versus-Host Disease and Bidirectional Immune Tolerance in Allogeneic Transplantation.
Innate Immune Determinants of Graft-Versus-Host Disease and Bidirectional Immune Tolerance in Allogeneic Transplantation.
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DOI：
10.21926/obm.transplant.1901044
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Pillai AB
中科院分区：
文献类型：
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作者：
Hamers AAJ;Joshi SK;Pillai AB
从健康供体到患病个体的组织移植（同种异体移植）的成功受到供体和受体的免疫系统的调节。在供者和受者之间形成一种特定的无反应状态，同时保持受者免疫功能的有益作用，称为“免疫（移植）耐受”。在典型的移植后早期，最大限度地减少双向供体←→受体反应性需要使用免疫抑制药物，这些药物具有有害的副作用（除了药物特异性反应和器官毒性外，还存在严重的免疫缺陷、机会性感染和肿瘤）。通过供体和受体免疫细胞直接诱导免疫耐受，特别是通过免疫调节细胞亚群，有助于显着减少同种异体移植后与多种免疫抑制药物相关的副作用。免疫系统的先天性和适应性臂都与诱导免疫耐受有关。在本文中，我们将回顾先天免疫子集操作及其在造血干细胞移植（HSCT）中的潜在应用，通过诱导长期的供体←→受体（双向）免疫耐受和减少移植物抗宿主病（GVHD）来治疗恶性和非恶性血液疾病。这些促进长期免疫同种异体移植耐受的先天免疫治疗策略包括骨髓源性抑制细胞（MDSC）、调节性巨噬细胞、耐受性树突状细胞（tDC）、自然杀伤（NK）细胞、不变自然杀伤T（iNKT）细胞、γδT（γδ-T）细胞和间充质基质细胞（MSC）。
The success of tissue transplantation from a healthy donor to a diseased individual (allo-transplantation) is regulated by the immune systems of both donor and recipient. Developing a state of specific non-reactivity between donor and recipient, while maintaining the salutary effects of immune function in the recipient, is called “immune (transplantation) tolerance”. In the classic early post-transplant period, minimizing bidirectional donor ←→ recipient reactivity requires the administration of immunosuppressive drugs, which have deleterious side effects (severe immunodeficiency, opportunistic infections, and neoplasia, in addition to drug-specific reactions and organ toxicities). Inducing immune tolerance directly through donor and recipient immune cells, particularly via subsets of immune regulatory cells, has helped to significantly reduce side effects associated with multiple immunosuppressive drugs after allo-transplantation. The innate and adaptive arms of the immune system are both implicated in inducing immune tolerance. In the present article, we will review innate immune subset manipulations and their potential applications in hematopoietic stem cell transplantation (HSCT) to cure malignant and non-malignant hematological disorders by inducing long-lasting donor ←→ recipient (bidirectional) immune tolerance and reduced graft-versus-host disease (GVHD). These innate immunotherapeutic strategies to promote long-term immune allo-transplant tolerance include myeloid-derived suppressor cells (MDSCs), regulatory macrophages, tolerogenic dendritic cells (tDCs), Natural Killer (NK) cells, invariant Natural Killer T (iNKT) cells, gamma delta T (γδ-T) cells and mesenchymal stromal cells (MSCs).