Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, United States.
Immunol Lett. 2013 Nov-Dec;156(1-2):94-101. doi: 10.1016/j.imlet.2013.09.008. Epub 2013 Sep 25.
The transcription factor Krüppel-like factor 4 (KLF4) can activate or repress gene expression in a cell-context dependent manner. We have previously shown that KLF4 inhibits the proliferation of naïve CD8(+) T cells in vitro downstream of the transcription factor ELF4. In this work, we describe a novel role of KLF4 in the differentiation of CD8(+) T cells upon infection. Loss of KLF4 had minimal effect on thymic T cell development and distribution of mature T cells in the spleen, blood, and lymph nodes. KLF4-deficient naïve CD8(+) T cells also displayed normal homeostatic proliferation upon adoptive transfer into lymphopenic hosts. However, activation of KLF4-deficient naïve CD8(+) T cells by in vitro TCR crosslink and co-stimulation resulted in increased proliferation. Furthermore, naïve KLF4-deficient OT-I CD8(+) T cells generated increased numbers of functional memory CD8(+) T cells compared to wild type OT-I CD8(+) T cells co-injected in the same recipient in both primary and recall responses to Listeria monocytogenes-OVA. Collectively, our data demonstrate that KLF4 regulates differentiation of functional memory CD8(+) T cells while sparing development and homeostasis of naïve CD8(+) T cells.
转录因子 Krüppel 样因子 4（KLF4）可以在依赖细胞环境的方式下激活或抑制基因表达。我们之前已经表明，KLF4 通过转录因子 ELF4 抑制幼稚 CD8(+)T 细胞在体外的增殖。在这项工作中，我们描述了 KLF4 在感染后 CD8(+)T 细胞分化中的一个新作用。缺失 KLF4 对胸腺 T 细胞发育和成熟 T 细胞在脾脏、血液和淋巴结中的分布几乎没有影响。KLF4 缺陷的幼稚 CD8(+)T 细胞在过继转移到淋巴耗竭宿主后也表现出正常的稳态增殖。然而，通过体外 TCR 交联和共刺激激活 KLF4 缺陷的幼稚 CD8(+)T 细胞会导致增殖增加。此外，与同受体中注射的野生型 OT-I CD8(+)T 细胞相比，幼稚的 KLF4 缺陷型 OT-I CD8(+)T 细胞在原发性和李斯特菌单核细胞增生症-OVA 的回忆反应中产生了更多数量的功能性记忆 CD8(+)T 细胞。总之，我们的数据表明 KLF4 调节功能性记忆 CD8(+)T 细胞的分化，同时保留幼稚 CD8(+)T 细胞的发育和稳态。
