Diabetes Center and Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
Nat Rev Immunol. 2016 Mar;16(3):149-63. doi: 10.1038/nri.2015.18. Epub 2016 Feb 15.
CD4(+) T cells differentiate and acquire distinct functions to combat specific pathogens but can also adapt their functions in response to changing circumstances. Although this phenotypic plasticity can be potentially deleterious, driving immune pathology, it also provides important benefits that have led to its evolutionary preservation. Here, we review CD4(+) T cell plasticity by examining the molecular mechanisms that regulate it - from the extracellular cues that initiate and drive cells towards varying phenotypes, to the cytosolic signalling cascades that decipher these cues and transmit them into the cell and to the nucleus, where these signals imprint specific gene expression programmes. By understanding how this functional flexibility is achieved, we may open doors to new therapeutic approaches that harness this property of T cells.
CD4(+) T 细胞分化并获得独特的功能来对抗特定的病原体,但也可以根据情况的变化来调整其功能。虽然这种表型可塑性可能具有潜在的有害性,导致免疫病理学,但它也提供了重要的益处,使其在进化中得以保存。在这里,我们通过研究调节 CD4(+) T 细胞可塑性的分子机制来回顾 CD4(+) T 细胞可塑性——从启动和驱动细胞向不同表型发展的细胞外信号,到解析这些信号并将其传递到细胞质中的信号级联,再到细胞核,这些信号在细胞核中印记特定的基因表达程序。通过了解如何实现这种功能灵活性,我们可能为利用 T 细胞这一特性的新治疗方法打开大门。