Amsen Derk, Spilianakis Charalampos G, Flavell Richard A
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Curr Opin Immunol. 2009 Apr;21(2):153-60. doi: 10.1016/j.coi.2009.03.010. Epub 2009 Apr 15.
Differentiation of T(H)1 and T(H)2 effector cells proceeds through several phases: First, naïve CD4(+) precursor cells are instructed to differentiate as appropriate to optimally fight the infectious threat encountered. This process is governed by the IL12 and IL4 cytokines, as well as by signaling through the Notch receptor. In response to these signals, transcription is initiated of lineage specific cytokine genes including the Ifngamma and Il4 genes as well as of genes encoding transcriptional regulators, such as T-bet and Gata3. The respective differentiation programs are reinforced by both positive and negative feedback mechanisms. Furthermore, epigenetic modifications of the lineage specific genes result in the emergence of regulatory elements, which control high level lineage restricted expression by both intrachromosomal and interchromosomal associations. Together, these mechanisms ensure stable inheritance of the differentiated fate in the numerous progeny of the original naïve CD4(+) T cells.
辅助性T细胞1（TH1）和辅助性T细胞2（TH2）效应细胞的分化过程历经多个阶段：首先，初始CD4(+)前体细胞会根据遇到的感染威胁进行适当分化，以实现最佳的对抗效果。这一过程受白细胞介素12（IL12）和白细胞介素4（IL4）细胞因子以及Notch受体信号传导的调控。作为对这些信号的响应，会启动谱系特异性细胞因子基因（包括Ifngamma和Il4基因）以及编码转录调节因子（如T-bet和Gata3）的基因的转录。各自的分化程序通过正反馈和负反馈机制得到加强。此外，谱系特异性基因的表观遗传修饰导致调控元件的出现，这些调控元件通过染色体内和染色体间的关联来控制高水平的谱系限制表达。这些机制共同确保了原始初始CD4(+) T细胞众多后代中分化命运的稳定遗传。
