Minor histocomplatibility antigens as targets of graft-versus-leukemia reactions
Minor histocomplatibility antigens as targets of graft-versus-leukemia reactions
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DOI：
10.1097/00062752-200211000-00005
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发表时间：
2002-11-01
影响因子：
3.2
通讯作者：
Willemze, R
中科院分区：
文献类型：
--
作者：
Falkenburg, JHF;Marijt, WAF;Willemze, R
异基因干细胞移植相对于自体干细胞移植用于恶性血液病的主要优点是在移植后使用供体来源的免疫效应细胞进行细胞免疫治疗的能力。在HILA匹配的异基因干细胞移植中，供体淋巴细胞的有益的移植物抗白血病效应似乎主要由能够识别来自患者的恶性细胞群体上的次要组织相容性抗原的同种异体反应性T细胞引起。次要组织相容性抗原的组织分布可能决定了T细胞对这些抗原反应的临床结果。识别广泛表达的抗原的T细胞不仅引起移植物抗白血病，而且引起移植物抗宿主病，而识别造血细胞上特异性表达的次要组织相容性抗原的T细胞可能主要消除受体的造血细胞，包括恶性细胞，而不影响供体造血或正常的非造血组织。移植物抗宿主病仍然可能发生，因为诱导了针对组织中造血细胞的炎症反应。移植后患者的疫苗接种或移植前使用次要组织相容性抗原特异性肽接种干细胞供体，离体产生次要组织相容性抗原特异性T细胞，以及通过T细胞受体的基因转移重定向T细胞特异性，可能是异基因干细胞移植后特异性根除恶性细胞的策略。(C)2002年利平科特威廉姆斯威尔金斯公司
The main advantage of allogeneic stem cell transplantation over autologous stem cell transplantation for hematologic malignancies is the ability to perform cellular immunotherapy using donor-derived immune effector cells after transplantation. In HILA-matched allogeneic stem cell transplantation, the beneficial graft-versus-leukemia effect of donor lymphocytes appears to be caused mainly by alloreactive T cells that are capable of recognizing minor histocompatibility antigens on the malignant cell population from the patient. The tissue distribution of minor histocompatibility antigens probably determines the clinical result of T-cell responses against these antigens. Whereas T cells recognizing broadly expressed antigens cause not only graft-versus-leukemia but also graft-versus-host disease, T cells recognizing minor histocompatibility antigens specifically expressed on hematopoietic cells may mainly eliminate hematopoietic cells from the recipient, including the malignant cells, without affecting donor hematopoiesis or normal nonhematopoietic tissues. Graft-versus-host disease may still occur because of the induction of inflammatory responses against hematopoietic cells in the tissues. Vaccination of patients after transplantation or vaccination of stem cell donors before transplantation using minor histocompatibility antigen-specific peptides, ex vivo production of minor histocompatibility antigen-specific T cells, and redirection of T-cell specificity by gene transfer of T-cell receptors may be strategies to eradicate specifically the malignant cells after allogeneic stem cell transplantation. (C) 2002 Lippincott Williams Wilkins, Inc.