Kelso A
Queensland Institute of Medical Research, University of Queensland, Post Office Royal Brisbane Hospital, Brisbane, Australia.
Springer Semin Immunopathol. 1999;21(3):231-48. doi: 10.1007/BF00812255.
T lymphocytes acquire the ability to synthesize cytokines during their primary response to antigen, often giving rise to effector populations with a polarized type 1 or type 2 cytokine profile. However, polarization is not a simple choice between two differentiation pathways. This article reviews the evidence, particularly from single-cell and clonal studies, that polarization is the outcome of a series of stochastic events whose probabilities are determined in part by genetic background and in part by extracellular signals received during activation and clonal expansion. The data suggest that these extracellular signals independently and differentially regulate the probability of expression of each cytokine gene, for example by their effects on clonal expansion and chromatin remodeling, CpG demethylation and transcriptional activation of cytokine genes. Polarization is, therefore, achieved at the population level by altering frequencies of expression among cells with many different expression patterns, rather than by selective differentiation of a discrete subset. Type 1 and type 2 populations progressively lose responsiveness to counter-polarizing stimuli. While the molecular basis of this process is not yet known, the observed persistence of cells with flexible cytokine profiles in some polarized populations suggests that loss of flexibility may also be a probabilistic event.
T淋巴细胞在对抗原的初次反应过程中获得合成细胞因子的能力，常常产生具有极化的1型或2型细胞因子谱的效应细胞群体。然而，极化并非两种分化途径之间的简单选择。本文综述了相关证据，尤其是来自单细胞和克隆研究的证据，即极化是一系列随机事件的结果，这些事件的概率部分由遗传背景决定，部分由激活和克隆扩增过程中接收到的细胞外信号决定。数据表明，这些细胞外信号独立且差异地调节每个细胞因子基因的表达概率，例如通过它们对克隆扩增、染色质重塑、细胞因子基因的CpG去甲基化和转录激活的影响。因此，极化是通过改变具有许多不同表达模式的细胞之间的表达频率在群体水平上实现的，而不是通过离散亚群的选择性分化。1型和2型群体逐渐失去对反极化刺激的反应性。虽然这一过程的分子基础尚不清楚，但在一些极化群体中观察到的具有灵活细胞因子谱的细胞的持续存在表明，灵活性的丧失也可能是一个概率性事件。
