Relevance of C1 and C2 epitopes for hemopoietic stem cell transplantation: Role for sequential acquisition of HLA-C-specific inhibitory killer Ig-like receptor
Relevance of C1 and C2 epitopes for hemopoietic stem cell transplantation: Role for sequential acquisition of HLA-C-specific inhibitory killer Ig-like receptor
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DOI：
10.4049/jimmunol.178.6.3918
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发表时间：
2007-03-15
影响因子：
4.4
通讯作者：
Uhrberg, Markus
中科院分区：
文献类型：
--
作者：
Fischer, Johannes C.;Ottinger, Hellmut;Uhrberg, Markus
本文对108例慢性粒细胞白血病非亲缘造血干细胞移植患者的杀伤Ig样受体（KIR）和HLA Ⅰ类配体进行了研究。在HLA-C编码的第1组（C1）配体纯合子患者中，与第2组（C2）配体纯合子患者相比，观察到总生存率显著改善。前一患者组的有利结局是早期效应，在移植G-CSF动员外周血的患者和晚期疾病患者中具有高度显著性。相比之下，供体中Cl配体的存在与患者存活率显著降低相关。这两个HLA-C配体的差异作用的背景下解释的偏见NK细胞重建，这是一般占主导地位的C1-但C2-特异性NK细胞的存在。通过体外实验证实了临床观察结果，体外实验显示，来源于造血祖细胞的NK细胞通常在更早的时间点获得Cl特异性抑制性KIR 2DL 2/3，并且频率高于C2特异性KIR 2DL 1。这些发现为理解NK细胞在临床造血干细胞移植中的作用提供了一个新的决定因素。
Killer Ig-like receptors (KIR) and HLA class I ligands were studied in unrelated hemopoietic stem cell transplantation for chronic myeloid leukemia (n = 108). Significantly improved overall survival was observed in patients, which were homozygous for HLA-C-encoded group 1 (C1) ligands compared with those with group 2 (C2) ligands. Favorable outcome in the former patient group was an early effect that was highly significant in patients transplanted with G-CSF-mobilized peripheral blood and patients with advanced disease stages. In contrast, presence of Cl ligands in the donor was associated with significantly reduced patient survival. The differential roles of the two HLA-C ligands are explained in the context of a biased NK cell reconstitution, which is generally dominated by the presence of C1- but absence of C2-specific NK cells. The clinical observations are corroborated by in vitro experiments showing that NK cells derived from hemopoietic progenitor cells generally acquire the Cl-specific inhibitory KIR2DL2/3 at earlier time points and with higher frequency than the C2-specific KIR2DL1. These findings define a novel determinant for understanding the role of NK cells in clinical hemopoietic stem cell transplantation.