Kallies Axel, Hawkins Edwin D, Belz Gabrielle T, Metcalf Donald, Hommel Mirja, Corcoran Lynn M, Hodgkin Philip D, Nutt Stephen L
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
Nat Immunol. 2006 May;7(5):466-74. doi: 10.1038/ni1321. Epub 2006 Mar 26.
T cell homeostasis is crucial for a functional immune system, as the accumulation of T cells resulting from lack of regulatory T cells or an inability to shut down immune responses can lead to inflammation and autoimmune pathology. Here we show that Blimp-1, a transcriptional repressor that is a 'master regulator' of terminal B cell differentiation, was expressed in a subset of antigen-experienced CD4(+) and CD8(+) T cells. Mice reconstituted with fetal liver stem cells expressing a mutant Blimp-1 lacking the DNA-binding domain developed a lethal multiorgan inflammatory disease caused by an accumulation of effector and memory T cells. These data identify Blimp-1 as an essential regulator of T cell homeostasis and suggest that Blimp-1 regulates both B cell and T cell differentiation.
T细胞稳态对于功能性免疫系统至关重要，因为缺乏调节性T细胞或无法关闭免疫反应导致的T细胞积累会引发炎症和自身免疫性病理。我们在此表明，转录抑制因子Blimp-1是终末B细胞分化的“主调控因子”，在一部分经历过抗原刺激的CD4(+)和CD8(+) T细胞中表达。用表达缺乏DNA结合结构域的突变型Blimp-1的胎肝干细胞重建的小鼠，因效应和记忆T细胞积累而患上致命的多器官炎症性疾病。这些数据确定Blimp-1是T细胞稳态的关键调节因子，并表明Blimp-1同时调节B细胞和T细胞分化。
