Dysfunctional memory CD8+ T cells after priming in the absence of the cell cycle regulator E2F4.
Dysfunctional memory CD8+ T cells after priming in the absence of the cell cycle regulator E2F4.
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DOI：
10.1016/j.cellimm.2009.02.006
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发表时间：
2009
影响因子：
4.3
通讯作者：
Crispe, Ian Nicholas
中科院分区：
文献类型：
--
作者：
Bancos, Simona;Cao, QingYu;Bowers, William J.;Crispe, Ian Nicholas
转录抑制因子E2 F4对于上皮细胞、神经元细胞和脂肪细胞的细胞周期退出和终末分化是重要的，但其在T淋巴细胞增殖和记忆形成中的作用尚不清楚。在此，我们研究了E2 F4蛋白在功能性小鼠记忆T细胞形成中的功能。用表达靶向E2 F4的shRNA的慢病毒载体体外感染鼠转基因CD 8 + T细胞，然后用SIINFEKL抗原肽体外刺激。对于体内测定，将转导的细胞注射到同源小鼠中，然后用HSV-OVA感染同源小鼠。测定CD 8+慢病毒转导细胞的初级应答、记忆形成和次级刺激。在缺乏E2 F4细胞周期阻遏物的情况下，活化的CD 8 + T细胞在体外和体内都经历了强烈的增殖。这些细胞具有在体内分化为记忆细胞的能力，但它们在回忆增殖方面有缺陷。我们发现，在CD 8 + T细胞引发过程中E2 F4的瞬时抑制增强了初级增殖，并对次级刺激产生负面影响。这些发现表明，细胞周期抑制因子E2 F4是形成功能性记忆T细胞所必需的。CD 8 + T淋巴细胞区室的减少将降低我们控制病毒感染的能力。
The transcriptional repressor E2F4 is important for cell cycle exit and terminal differentiation in epithelial cells, neuronal cells and adipocytes but its role in T lymphocytes proliferation and memory formation is not known. Herein, we investigated the function of E2F4 protein for the formation of functional murine memory T cells. Murine transgenic CD8+ T cells were infected in vitro with lentivirus vector expressing a shRNA targeted against E2F4 followed by in vitro stimulation with SIINFEKL antigenic peptide. For in vivo assays, transduced cells were injected into congenic mice which were then infected with HSV-OVA. The primary response, memory formation and secondary stimulation were determined for CD8+ lentivirus transduced cells. In the absence of E2F4 cell cycle repressor, activated CD8+ T cells underwent intensive proliferation in vitro and in vivo. These cells had the ability to differentiate into memory cells in vivo, but they were defective in recall proliferation. We show that transient suppression of E2F4 during CD8+ T cell priming enhances primary proliferation and has a negative effect on secondary stimulation. These findings demonstrate that the cell cycle repressor E2F4 is essential for the formation of functional memory T cells. A decrease in CD8+ T-lymphocyte compartment would diminish our capacity to control viral infections.
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