KIR reconstitution is altered by T cells in the graft and correlates with clinical outcomes after unrelated donor transplantation
KIR reconstitution is altered by T cells in the graft and correlates with clinical outcomes after unrelated donor transplantation
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DOI：
10.1182/blood-2005-04-1644
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发表时间：
2005-12-15
期刊：
影响因子：
20.3
通讯作者：
Miller, JS
中科院分区：
文献类型：
--
作者：
Cooley, S;McCullar, V;Miller, JS
尽管无关造血细胞移植（HCT）可以治愈许多血液恶性肿瘤，但并发症和复发仍然是具有挑战性的障碍。自然杀伤（NK）细胞在移植后迅速恢复，产生细胞因子并表达调节其细胞毒性的杀伤免疫球蛋白样受体（KIR）。一些基于 KIR 配体错配策略的临床试验与减少复发和提高生存率相关，但结果好坏参半。我们假设移植物中的 T 细胞可能会影响无关移植后的 NK 细胞功能和 KIR 表达，并且这些差异与临床结果相关。使用来自国家骨髓捐赠计划研究存储库的 77 个配对样本评估 NK 细胞功能。将未经操作的骨髓 (UBM) 和 T 细胞耗尽 (TCD) 移植后 100 天的受体 NK 细胞与来自健康捐赠者的 NK 细胞进行比较。与 TCD 移植相比，UBM 后 NK 细胞表达更少的 KIR，并产生更多的干扰素 γ (IFN-gamma)。多变量模型表明，NK 细胞 IFN-γ 产生的增加与更急性的移植物抗宿主病 (GVHD) 相关，而 KIR 表达的减少与较差的生存率相关。这些结果支持移植物中的 T 细胞影响体内 NK 细胞重建的观点。了解这些机制可能会产生改善不相关 HCT 临床结果的策略。
Although unrelated hematopoietic cell transplantation (HCT) is curative for many hematologic malignancies, complications and relapse remain challenging obstacles. Natural killer (NK) cells, which recover quickly after transplantation, produce cytokines and express killer immunoglobulin-like receptors (KIRs) that regulate their cytotoxicity. Some clinical trials based on a KIR ligand mismatch strategy are associated with less relapse and increased survival, but results are mixed. We hypothesized that T cells in the graft may affect NK cell function and KIR expression after unrelated transplantation and that these differences correlate with clinical outcomes. NK cell function was evaluated using 77 paired samples from the National Marrow Donor Program Research Repository. Recipient NK cells at 100 days after both unmanipulated bone marrow (UBM) and T-cell depleted (TCD) transplants were compared with NK cells from their healthy donors. NK cells expressed fewer KIRs and produced more interferon gamma (IFN-gamma) after UBM compared to TCD transplants. Multivariate models showed that increased NK cell IFN-gamma production correlated with more acute graft-versus-host disease (GVHD), and decreased KIR expression correlated with Inferior survival. These results support the notion that T cells in the graft affect NK cell reconstitution in vivo. Understanding these mechanisms may result in strategies to improve clinical outcomes from unrelated HCT.