Clinical relapses of multiple sclerosis are associated with 'novel' valleys in natural killer cell functional activity
Clinical relapses of multiple sclerosis are associated with 'novel' valleys in natural killer cell functional activity
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DOI：
10.1016/j.jneuroim.2003.10.001
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发表时间：
2003-12-01
影响因子：
3.3
通讯作者：
Paty, DW
中科院分区：
文献类型：
--
作者：
Kastrukoff, LF;Lau, A;Paty, DW
自然杀伤（NK）细胞与多发性硬化（MS）的发病机制有关。9例复发缓解型MS（RRMS）患者沿着年龄、性别和NK应答状态匹配的对照进行了系列研究。虽然两组间的平均NK细胞功能活性（FA）没有显著差异，但RRMS患者的4次临床复发与FA中“新”谷的发展相关。在RRMS和对照组中，FA的周期性峰和谷由CD 33（+）、CD 3（-）、CD 56（+）、CD 38（-）、CD 39（-）和CD 39（-）的数量决定。以及在较小程度上能够结合靶并诱导细胞介导的细胞毒性（CMC）的CD 3（+）CD 56（+）细胞。相反，FA中的“新”谷是由于与靶点结合的CD 3（-）CD 56（+）诱导CMC的能力降低所致。结果表明，在FA中的“新”谷期间，RRMS患者临床复发的风险更大。此外，这些谷是具有NK细胞表型的细胞无法对靶点进行“致命”打击的结果。(C)2003 Elsevier B.V保留所有权利。
Natural killer (NK) cells are implicated in the pathogenesis of multiple sclerosis (MS). Nine relapsing-remitting MS (RRMS) patients along with age, sex, and NK responder status matched controls were studied serially. Although the average NK cell functional activity (FA) was not significantly different between both groups, four clinical relapses in RRMS patients were associated with the development of 'novel' valleys in FA. These valleys are of greater depth and duration than cyclical valleys observed in both RRMS and controls, precede the onset of clinical attacks, and are observed in RRMS but not controls.In both RRMS and controls, cyclical peaks and valleys in FA are determined by the number of CD33(+), CD3(-)CD56(+), and to a lessor extent CD3(+)CD56(+) cells capable of binding targets and inducing cell-mediated cytotoxicity (CMC). In contrast, 'novel' valleys in FA result from a reduction in the ability of CD3(-)CD56(+) bound to targets to induce CMC.The results suggest that RRMS patients are at greater risk for clinical relapses during 'novel' valleys in FA. Furthermore, these valleys are the result of cells with a NK cell phenotype being unable to deliver a 'lethal' hit to targets. (C) 2003 Elsevier B.V All rights reserved.