Evidence of B cell immune responses to acute lymphoblastic leukemia in murine allogeneic hematopoietic stem cell transplantation recipients treated with donor lymphocyte infusion and/or vaccination.
Evidence of B cell immune responses to acute lymphoblastic leukemia in murine allogeneic hematopoietic stem cell transplantation recipients treated with donor lymphocyte infusion and/or vaccination.
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在接受供体淋巴细胞输注和/或疫苗接种治疗的小鼠同种异体造血干细胞移植受者中，B 细胞对急性淋巴细胞白血病产生免疫反应的证据。
DOI：
10.1016/j.bbmt.2010.08.021
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Hsu,Yu-Chiao
中科院分区：
文献类型：
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作者：
Mullen,CraigA;Campbell,Andrew;Tkachenko,Olena;Jansson,Johan;Hsu,Yu-Chiao
这些实验探索了异基因造血干细胞移植后控制急性淋巴细胞性白血病(ALL)的机制，采用的是MHC相合、组织相容性较差的抗原不匹配移植的小鼠模型。研究的中心假设是，增加针对白血病细胞的主动疫苗接种将显著增加异基因供者淋巴细胞输注(DLI)对移植后宿主中存在的ALL的有效性。尽管接种疫苗确实增加了针对与DLI相关的白血病细胞的I型T细胞反应的幅度，但它并没有导致长期存活率的实质性改善。对白血病进展的免疫学机制分析表明，免疫失败不是由于白血病细胞中的抗原丢失所致。然而，生存分析提供了令人惊讶的发现，除了非常温和的I型T细胞反应外，在长期幸存者中发现了产生与白血病细胞结合的抗体的B细胞反应。这种抗体水平较高的受者死于白血病的风险明显较低。这些研究提出的假设是，移植后刺激B细胞反应可能提供一种新的方法来增强与移植相关的同种异体移植物抗白血病效果。
These experiments explored mechanisms of control of acute lymphoblastic leukemia (ALL) following allogeneic hematopoietic stem cell transplantation using a murine model of MHC-matched, minor histocompatibility antigen–mismatched transplantation. The central hypothesis examined was that addition of active vaccination against leukemia cells would substantially increase the effectiveness of allogeneic donor lymphocyte infusion (DLI) against ALL present in the host after transplantation. Although vaccination did increase the magnitude of type I T cell responses against leukemia cells associated with DLI, it did not lead to substantial improvement in long-term survival. Analysis of immunologic mechanisms of leukemia progression demonstrated that the failure of vaccination was not because of antigen loss in leukemia cells. However, analysis of survival provided surprising findings that, in addition to very modest type I T cell responses, a B cell response that produced antibodies that bind leukemia cells was found in long-term survivors. The risk of death from leukemia was significantly lower in recipients that had higher levels of such antibodies. These studies raise the hypothesis that stimulation of B cell responses after transplantation may provide a novel way to enhance allogeneic graft-versus-leukemia effects associated with transplantation.