Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University, North Chicago, IL, United States.
Front Immunol. 2019 Feb 15;10:184. doi: 10.3389/fimmu.2019.00184. eCollection 2019.
CD8 T cell differentiation orchestrated by transcription regulators is critical for balancing pathogen eradication and long-term immunity by effector and memory CTLs, respectively. The transcription factor Nuclear Factor of Activated T cells (NFAT) family members are known for their roles in T cell development and activation but still largely undetermined in CD8 T cell differentiation . Here, we interrogated the role of two NFAT family members, NFAT1 and NFAT2, in the effector and memory phase of CD8 T cell differentiation using LCMV acute infection model. We found that NFAT1 is critical for effector population generation whereas NFAT2 is required for promoting memory CTLs in a cell intrinsic manner. Moreover, we found that mice lacking both NFAT1 and NFAT2 in T cells display a significant increase in KLRG1 CD127 population and are unable to clear an acute viral infection. NFAT-deficient CTLs showed different degrees of impaired IFN-γ and TNF-α expression with NFAT1 being mainly responsible for IFN-γ production upon stimulation as well as for antigen-specific cytotoxicity. Our results suggest that NFAT1 and NFAT2 have distinct roles in mediating CD8 T cell differentiation and function.
转录因子激活 T 细胞的核因子（NFAT）家族成员在 T 细胞的发育和激活中起关键作用，但在 CD8 T 细胞分化中其作用仍很大程度上未被确定。在这里，我们使用 LCMV 急性感染模型研究了两个 NFAT 家族成员 NFAT1 和 NFAT2 在 CD8 T 细胞分化的效应器和记忆阶段的作用。我们发现 NFAT1 对于效应细胞群体的产生至关重要，而 NFAT2 以细胞内在的方式促进记忆 CTL。此外，我们发现 T 细胞中缺乏 NFAT1 和 NFAT2 的小鼠中 KLRG1 CD127 群体显著增加，并且无法清除急性病毒感染。NFAT 缺陷型 CTL 的 IFN-γ 和 TNF-α表达受到不同程度的损害，其中 NFAT1 主要负责刺激后的 IFN-γ产生以及抗原特异性细胞毒性。我们的结果表明，NFAT1 和 NFAT2 在介导 CD8 T 细胞分化和功能方面具有不同的作用。
