Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent function
Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent function
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DOI：
10.1182/blood-2011-10-386995
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发表时间：
2012-03-15
期刊：
影响因子：
20.3
通讯作者：
Miller, Jeffrey S.
中科院分区：
文献类型：
--
作者：
Foley, Bree;Cooley, Sarah;Miller, Jeffrey S.
在小鼠巨细胞病毒（CMV）感染期间，Ly 49 H（+）自然杀伤（NK）细胞群体扩增，并通过诱导“记忆NK细胞应答”负责疾病清除。“人类CMV感染是否发生类似事件尚不清楚。在本研究中，我们的特点是在造血细胞移植后的人受体的巨细胞病毒再激活的NK细胞反应的动力学。在急性感染期间，NKG 2C（+）NK细胞扩增并成为IFN γ的强效生产者。NKG 2C（+）NK细胞主要表达杀伤细胞免疫球蛋白样受体，而自身杀伤细胞免疫球蛋白样受体是IFN γ产生所必需的。在移植后的第一年期间，CMV再激活诱导了以CD 56 dim NK细胞增加为特征的更成熟的表型。引人注目的是，NKG 2C（+）NK细胞的频率增加持续存在，并在CMV再激活的受体中继续增加，而这些细胞在没有CMV再激活的受体中保持低频率。持续存在的NKG 2C（+）NK细胞缺乏NKG 2A，表达CD 158 b，优先获得CD 57，并且在移植后第一年内是IFN γ的强效生产者。再激活CMV的受体也表达了更高量的IFN γ、T-bet和IL-15 R α mRNA转录物。我们的研究结果支持了CMV诱导的先天记忆细胞群可能有助于移植后长期恶性疾病复发保护和传染病控制的新概念。（血。2012;119（11）：2665-2674）
During mouse cytomegalovirus (CMV) infection, a population of Ly49H(+) natural killer (NK) cells expands and is responsible for disease clearance through the induction of a "memory NK-cell response." Whether similar events occur in human CMV infection is unknown. In the present study, we characterized the kinetics of the NK-cell response to CMV reactivation in human recipients after hematopoietic cell transplantation. During acute infection, NKG2C(+) NK cells expanded and were potent producers of IFN gamma. NKG2C(+) NK cells predominately ex-pressed killer cell immunoglobulin-like receptor, andself-killer cell immunoglobulin-like receptors were required for robust IFN gamma production. During the first year after transplantation, CMV reactivation induced a more mature phenotype characterized by an increase in CD56dim NK cells. Strikingly, increased frequencies of NKG2C(+) NK cells persisted and continued to increase in recipients who reactivated CMV, whereas these cells remained at low frequency in recipients without CMV reactivation. Persisting NKG2C(+) NK cells lacked NKG2A, expressed CD158b, preferentially acquired CD57, and were potent producers of IFN gamma during the first year after transplantation. Recipients who reactivated CMV also expressed higher amounts of IFN gamma, T-bet, and IL-15R alpha mRNA transcripts. Our findings support the emerging concept that CMV-induced innate memory-cell populations may contribute to malignant disease relapse protection and infectious disease control long after transplantation. (Blood. 2012;119(11):2665-2674)