Genetic and environmental determinants of human NK cell diversity revealed by mass cytometry.
Genetic and environmental determinants of human NK cell diversity revealed by mass cytometry.
复制标题
DOI：
10.1126/scitranslmed.3006702
复制
发表时间：
2013-10-23
影响因子：
17.1
通讯作者：
Blish CA
中科院分区：
文献类型：
--
作者：
Horowitz A;Strauss-Albee DM;Leipold M;Kubo J;Nemat-Gorgani N;Dogan OC;Dekker CL;Mackey S;Maecker H;Swan GE;Davis MM;Norman PJ;Guethlein LA;Desai M;Parham P;Blish CA
自然杀伤（NK）细胞在免疫防御和生殖中起着关键作用，但仍然是最知之甚少的主要淋巴细胞群体。因为它们的活化是由多种组合表达的活化和抑制受体控制的，所以NK细胞的多样性和功能是密切相关的。为了提供一个前所未有的理解NK细胞库的多样性，我们使用大量的细胞计数术，同时分析35个参数，包括28个NK细胞受体，外周血NK细胞从5套单卵双胞胎和12个无关的捐助者定义的HLA和杀伤细胞免疫球蛋白样受体（KIR）基因型。该分析揭示了显著程度的NK细胞多样性，在个体内估计有6，000 - 30，000个表型群体，并且在该群体中有> 100，000个表型。遗传学在很大程度上决定了抑制性受体的表达，而激活受体的表达受到环境的严重影响。因此，NK细胞可以通过严格调节抑制性受体的表达来维持自身耐受性，同时使用活化和共刺激受体的适应性表达模式来响应病原体和肿瘤。这些研究结果进一步表明，离散的NK细胞亚群可以用于感染，生殖和移植环境中的免疫策略的可能性。
Natural Killer (NK) cells play critical roles in immune defense and reproduction, yet remain the most poorly understood major lymphocyte population. Because their activation is controlled by a variety of combinatorially expressed activating and inhibitory receptors, NK cell diversity and function are closely linked. To provide an unprecedented understanding of NK cell repertoire diversity, we used mass cytometry to simultaneously analyze 35 parameters, including 28 NK cell receptors, on peripheral blood NK cells from five sets of monozygotic twins and twelve unrelated donors of defined HLA and killer cell immunoglobulin-like receptor (KIR) genotype. This analysis revealed a remarkable degree of NK cell diversity, with an estimated 6,000-30,000 phenotypic populations within an individual and >100,000 phenotypes in this population. Genetics largely determined inhibitory receptor expression, whereas activation receptor expression was heavily environmentally influenced. Therefore, NK cells may maintain self-tolerance through strictly regulated expression of inhibitory receptors, while using adaptable expression patterns of activating and costimulatory receptors to respond to pathogens and tumors. These findings further suggest the possibility that discrete NK cell subpopulations could be harnessed for immunotherapeutic strategies in the settings of infection, reproduction, and transplantation.
登录
查看更多内容
影响因子：
7.3
作者：
Cichocki F;Miller JS;Anderson SK;Bryceson YT
通讯作者：
Bryceson YT
影响因子：
0.9
作者：
Krasnow, Ruth E.;Jack, Lisa M.;Swan, Gary E.
通讯作者：
Swan, Gary E.
影响因子：
5.4
作者：
BIRON, CA;WELSH, RM
通讯作者：
WELSH, RM
影响因子：
6.4
作者：
Jost, Stephanie;Reardon, Jeff;Altfeld, Marcus
通讯作者：
Altfeld, Marcus
DOI：
10.1126/science.1198704
发表时间：
2011-05-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bendall SC;Simonds EF;Qiu P;Amir el-AD;Krutzik PO;Finck R;Bruggner RV;Melamed R;Trejo A;Ornatsky OI;Balderas RS;Plevritis SK;Sachs K;Pe'er D;Tanner SD;Nolan GP
通讯作者：
Nolan GP