The Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
Nat Immunol. 2010 Aug;11(8):709-16. doi: 10.1038/ni.1898. Epub 2010 Jul 4.
Several gene-deficiency models promote the development of innate CD8(+) T cells that have diverse T cell antigen receptors (TCRs) but have a memory phenotype and rapidly produce cytokines. We demonstrate here that similar cells developed in mice deficient in the transcription factor KLF2. However, this was not due to intrinsic deficiency in KLF2 but instead was due to interleukin 4 (IL-4) produced by an expanded population of T cells expressing the transcription factor PLZF. The development of innate CD8(+) T cells in mice deficient in the tyrosine kinase Itk and coactivator CBP was also attributable to this IL-4-dependent mechanism. Finally, we show that the same mechanism drove the differentiation of innate CD8(+) T cells in BALB/c mice. Our findings identify a previously unknown mechanism of regulation of CD8(+) T cells via the production of IL-4 by PLZF(+) T cells.
几种基因缺陷模型促进了先天 CD8(+)T 细胞的发育，这些细胞具有多样化的 T 细胞抗原受体（TCR），但具有记忆表型，并能快速产生细胞因子。我们在这里证明，在转录因子 KLF2 缺失的小鼠中也会产生类似的细胞。然而，这并不是由于 KLF2 的内在缺陷，而是由于表达转录因子 PLZF 的 T 细胞群体扩增所产生的白细胞介素 4（IL-4）。酪氨酸激酶 Itk 和共激活因子 CBP 缺失的小鼠中先天 CD8(+)T 细胞的发育也归因于这种依赖 IL-4 的机制。最后，我们表明相同的机制驱动了 BALB/c 小鼠中先天 CD8(+)T 细胞的分化。我们的发现确定了一种通过 PLZF(+)T 细胞产生白细胞介素 4 来调节 CD8(+)T 细胞的先前未知机制。
