Department of Pathology, Johns Hopkins University, United States.
The Graduate Program in Immunology, USA; Medical Scientist Training Program, USA.
Cell Immunol. 2020 Nov;357:104210. doi: 10.1016/j.cellimm.2020.104210. Epub 2020 Sep 5.
While memory T-cells represent a hallmark of adaptive immunity, little is known about the genetic mechanisms regulating the longevity of memory CD4 T cells. Here, we studied the dynamics of gene expression in antigen specific CD4 T cells during infection, memory differentiation, and long-term survival up to nearly a year in mice. We observed that differentiation into long lived memory cells is associated with increased expression of genes inhibiting cell proliferation and apoptosis as well as genes promoting DNA repair response, lipid metabolism, and insulin resistance. We identified several transmembrane proteins in long-lived murine memory CD4 T cells, which co-localized exclusively within the responding antigen-specific memory CD4 T cells in human. The unique gene signatures of long-lived memory CD4 T cells, along with the new markers that we have defined, will enable a deeper understanding of memory CD4 T cell biology and allow for designing novel vaccines and therapeutics.
虽然记忆 T 细胞代表了适应性免疫的一个标志，但对于调节记忆 CD4 T 细胞寿命的遗传机制知之甚少。在这里，我们研究了在感染、记忆分化和长达近一年的长期存活过程中抗原特异性 CD4 T 细胞中基因表达的动态变化。我们观察到，分化为长寿记忆细胞与抑制细胞增殖和凋亡的基因以及促进 DNA 修复反应、脂质代谢和胰岛素抵抗的基因的表达增加有关。我们在长寿的小鼠记忆 CD4 T 细胞中鉴定了几种跨膜蛋白，这些蛋白仅在人类的反应性抗原特异性记忆 CD4 T 细胞内共定位。长寿记忆 CD4 T 细胞的独特基因特征，以及我们定义的新标记，将使我们能够更深入地了解记忆 CD4 T 细胞生物学，并为设计新型疫苗和治疗方法提供依据。
