Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):E6097-E6106. doi: 10.1073/pnas.1705065114. Epub 2017 Jul 10.
The immune system consists of many specialized cell populations that communicate with each other to achieve systemic immune responses. Our analyses of various measured immune cell population frequencies in healthy humans and their responses to diverse stimuli show that human immune variation is continuous in nature, rather than characterized by discrete groups of similar individuals. We show that the same three key combinations of immune cell population frequencies can define an individual's immunotype and predict a diverse set of functional responses to cytokine stimulation. We find that, even though interindividual variations in specific cell population frequencies can be large, unrelated individuals of younger age have more homogeneous immunotypes than older individuals. Across age groups, cytomegalovirus seropositive individuals displayed immunotypes characteristic of older individuals. The conceptual framework for defining immunotypes suggested by our results could guide the development of better therapies that appropriately modulate collective immunotypes, rather than individual immune components.
免疫系统由许多具有专业知识的细胞群体组成，这些细胞群体相互沟通以实现全身免疫反应。我们分析了健康人类的各种测量免疫细胞群体频率及其对各种刺激的反应，结果表明人类免疫变异本质上是连续的，而不是由类似个体的离散群体来表征。我们表明，相同的三种关键免疫细胞群体频率组合可以定义个体的免疫类型，并预测对细胞因子刺激的多种功能反应。我们发现，尽管特定细胞群体频率的个体间变化可能很大，但年龄较小的无关个体的免疫类型比年龄较大的个体更相似。在各个年龄组中，巨细胞病毒血清阳性个体表现出与老年个体特征相符的免疫类型。我们的研究结果提出的定义免疫类型的概念框架可以指导更好的治疗方法的开发，这些方法可以适当调节集体免疫类型，而不是个体免疫成分。
