Graft-vs.-host and graft-vs.-leukemia reactions after delayed infusions of donor T-subsets.
Graft-vs.-host and graft-vs.-leukemia reactions after delayed infusions of donor T-subsets.
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DOI：
10.1053/bbmt.1999.v5.pm10392958
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发表时间：
1999-01-01
期刊：
影响因子：
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通讯作者：
Truitt, R L
中科院分区：
文献类型：
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作者：
Johnson, B D;Becker, E E;Truitt, R L
在移植后，已向异基因骨髓接受者输注供体白细胞以治疗白血病复发。用这些供体细胞的延迟输注进行的治疗被称为延迟或供体白细胞输注（DLI）。虽然移植物vs.-尽管宿主疾病（GVHD）在DLI后通常没有预期的严重，但它仍然是一个重要的风险因素。最近，我们使用了一个完整的主要组织相容性复合体（MHC）错配模型（C57 BL/6到AKR），以确定增加的免疫遗传差异如何影响GVH和移植物-vs. DLI后的白血病（GVL）反应。与MHC-匹配模型（B10.BR进入AKR）相反，当移植后3周输注MHC-不匹配的供体T细胞时，仍观察到GVHD。有限稀释分析用于确定同种异体反应性细胞毒性T淋巴细胞（CTL）和白细胞介素（IL）-2分泌的T辅助细胞在MHC不匹配的受者的脾脏DLI治疗后7天的频率。移植物抗宿主病与同种异体反应性辅助性T细胞频率升高相关。降低DLI后GVHD严重程度的一种策略是选择性施用CD 4或CD 8 T亚群。移植后3周延迟输注纯化的T细胞亚群导致GVHD显著低于输注两个亚群的混合物。用纯化的供体CD 4 + T细胞DLI后未观察到GVH相关的死亡率。在GVL研究中，MHC错配的CD 8 + T细胞是针对急性T细胞白血病的最有效的抗肿瘤效应物。将MHC不匹配的T亚群与MHC匹配的T亚群的GVL效应进行比较。当初始MHC匹配细胞作为DLI给予时，任一T亚群的耗竭消除了GVL效应。然而，来自MHC匹配供体的CD 8 + T细胞针对宿主同种异体抗原引发，介导了CD 4（辅助性T细胞）非依赖性GVL反应。总之，这些结果表明，给予T亚群可以显著减少DLI后的GVHD，而不会损失有益的GVL效应。
Infusions of donor leukocytes have been given to allogeneic bone marrow recipients after transplant to treat leukemia relapse. Treatment with these delayed infusions of donor cells has been called delayed or donor leukocyte infusion (DLI). While graft-vs.-host disease (GVHD) has typically been less severe than expected after DLI, it still remains a significant risk factor. Recently, we used a full major histocompatibility complex (MHC)-mismatched model (C57BL/6 into AKR) to determine how increased immunogenetic disparity affects GVH and graft-vs.-leukemia (GVL) reactions after DLI. In contrast to an MHC-matched model (B10.BR into AKR), GVHD was still observed when MHC-mismatched donor T cells were infused 3 weeks posttransplant. Limiting dilution analysis was used to determine the frequency of alloreactive cytotoxic T lymphocytes (CTL) and interleukin (IL)-2-secreting T helper cells in the spleens of MHC-mismatched recipients 7 days after DLI treatment. GVHD correlated with elevated frequencies of alloreactive T-helper cells. One strategy for reducing the severity of GVHD after DLI is the selective administration of CD4 or CD8 T-subsets. Delayed infusion of purified T-subsets 3 weeks posttransplant resulted in significantly less GVHD than infusion of a mixture of the two subsets. No GVH-associated mortality was observed after DLI with purified donor CD4+ T cells. In GVL studies, MHC-mismatched CD8+ T cells were the most potent antitumor effectors against an acute T cell leukemia. The GVL effect of MHC-mismatched T-subsets was compared with that of MHC-matched subsets. When naive MHC-matched cells were given as DLI, depletion of either T-subset eliminated the GVL effect. CD8+ T cells from MHC-matched donors primed against host alloantigens, however, mediated a CD4 (T-helper)-independent GVL reaction. Together, these results suggest that administration of T-subsets can significantly reduce GVHD after DLI without loss of the beneficial GVL effect.