Ansel K Mark, Lee Dong U, Rao Anjana
Center for Blood Research, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA.
Nat Immunol. 2003 Jul;4(7):616-23. doi: 10.1038/ni0703-616.
Antigen and cytokine receptor signals act in synergy to direct the differentiation of CD4+ T cells. These signals initiate reciprocal activation and silencing of the interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) cytokine gene loci, changes that are heritably maintained in the resulting T helper type 1 (T(H)1) or T(H)2 cells and their progeny. Early, unpolarized transcription and chromatin remodeling of the poised cytokine genes of naive T cells is followed by consolidation and spreading of epigenetic changes and the establishment of self-reinforcing transcription factor networks. Recent studies have begun to elucidate the molecular mechanisms that establish and maintain polarized cytokine gene expression, and thus the cellular identity of differentiated helper T cells.
抗原和细胞因子受体信号协同作用，指导CD4+ T细胞的分化。这些信号启动干扰素-γ（IFN-γ）和白细胞介素4（IL-4）细胞因子基因位点的相互激活和沉默，这些变化在产生的1型辅助性T细胞（T(H)1）或2型辅助性T细胞（T(H)2）及其后代中可遗传地维持。幼稚T细胞中处于准备状态的细胞因子基因的早期、未极化转录和染色质重塑之后，是表观遗传变化的巩固和扩展以及自我强化转录因子网络的建立。最近的研究已经开始阐明建立和维持极化细胞因子基因表达的分子机制，从而阐明分化的辅助性T细胞的细胞特性。
