Varanasi Siva Karthik, Jaggi Ujjaldeep, Hay Nissim, Rouse Barry T
Department of Genome Science and Technology, University of Tennessee, Knoxville, Tennessee, United States of America.
Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee, United States of America.
PLoS One. 2018 Jan 19;13(1):e0191533. doi: 10.1371/journal.pone.0191533. eCollection 2018.
Activation of CD4 T cells leads to their metabolic reprogramming which includes enhanced glycolysis, catalyzed through hexokinase enzymes. Studies in some systems indicate that the HK2 isoform is the most up regulated isoform in activated T cells and in this report the relevance of this finding is evaluated in an infectious disease model. Genetic ablation of HK2 was achieved in only T cells and the outcome was evaluated by measures of T cell function. Our results show that CD4 T cells from both HK2 depleted and WT animals displayed similar responses to in vitro stimulation and yielded similar levels of Th1, Treg or Th17 subsets when differentiated in vitro. A modest increase in the levels of proliferation was observed in CD4 T cells lacking HK2. Deletion of HK2 led to enhanced levels of HK1 indicative of a compensatory mechanism. Finally, CD4 T cell mediated immuno-inflammatory responses to a virus infection were similar between WT and HK2 KO animals. The observations that the expression of HK2 appears non-essential for CD4 T cell responses against virus infections is of interest since it suggests that targeting HK2 for cancer therapy may not have untoward effects on CD4 T cell mediated immune response against virus infections.
CD4 T细胞的激活会导致其代谢重编程，其中包括通过己糖激酶催化的糖酵解增强。一些系统的研究表明，HK2亚型是活化T细胞中上调最多的亚型，在本报告中，在传染病模型中评估了这一发现的相关性。仅在T细胞中实现了HK2的基因敲除，并通过T细胞功能指标评估结果。我们的结果表明，来自HK2缺失动物和野生型动物的CD4 T细胞对体外刺激表现出相似的反应，并且在体外分化时产生相似水平的Th1、Treg或Th17亚群。在缺乏HK2的CD4 T细胞中观察到增殖水平有适度增加。HK2的缺失导致HK1水平升高，表明存在一种补偿机制。最后，野生型和HK2基因敲除动物之间，CD4 T细胞介导的对病毒感染的免疫炎症反应相似。HK2的表达对于CD4 T细胞对病毒感染的反应似乎并非必不可少，这一观察结果很有趣，因为它表明针对HK2进行癌症治疗可能不会对CD4 T细胞介导的针对病毒感染的免疫反应产生不良影响。
