小柯机器人

近日，美国明尼苏达大学David Masopust及其研究团队发现，功能性T细胞具有额外细胞分裂和长寿潜力。2023年1月18日，《自然》杂志在线发表了这项成果。

研究人员讨论了T细胞是否受到时间或细胞分裂限制的内在限制。研究人员在体内用急性异种抗原启动-增强-增强疫苗激活小鼠T细胞时，将扩增的细胞转移到新小鼠体内，然后重复这一过程。在超过10年（大大超过小鼠的寿命）和51轮连续免疫，T细胞仍然有能力对疫苗接种作出反应。细胞在刺激事件之间需要充分休息。尽管显示出将起始群体扩大至少10⁴⁰倍的潜力，细胞并没有表现出增殖控制的丧失，结果也不是由于年轻细胞的污染。慢性感染或癌症的持续刺激可引起T细胞增殖、衰老、功能衰竭和死亡。研究人员发现，尽管反复的急性刺激也会在细胞中诱导常见排气标记物（包括PD1，也称为PDCD1和TOX）的表达和表观遗传重塑，但它们仍然可以增殖，执行抗菌功能并形成静态记忆细胞。这些观察为更好地理解记忆细胞分化、衰竭、癌症和衰老提供了一个模型，并表明功能强大的T细胞可以在其有机体寿命之外保持非凡的种群扩张和寿命的潜力。

据悉，分化的体细胞哺乳动物细胞被认为表现出物种特异性的分裂限制，可以阻止癌症，但可能限制寿命。为了提供免疫，短暂刺激的CD8⁺T细胞经历了不稳定的快速细胞分裂，然后形成静态的长寿命记忆细胞，在随后的免疫挑战中保持重新增殖的状态。

附：英文原文

Title: Functional T cells are capable of supernumerary cell division and longevity

Author: Soerens, Andrew G., Knzli, Marco, Quarnstrom, Clare F., Scott, Milcah C., Swanson, Lee, Locquiao, JJ., Ghoneim, Hazem E., Zehn, Dietmar, Youngblood, Benjamin, Vezys, Vaiva, Masopust, David

Issue&Volume: 2023-01-18

Abstract: Differentiated somatic mammalian cells putatively exhibit species-specific division limits that impede cancer but may constrain lifespans1,2,3. To provide immunity, transiently stimulated CD8+ T cells undergo unusually rapid bursts of numerous cell divisions, and then form quiescent long-lived memory cells that remain poised to reproliferate following subsequent immunological challenges. Here we addressed whether T cells are intrinsically constrained by chronological or cell-division limits. We activated mouse T cells in vivo using acute heterologous prime–boost–boost vaccinations4, transferred expanded cells to new mice, and then repeated this process iteratively. Over 10 years (greatly exceeding the mouse lifespan)5 and 51 successive immunizations, T cells remained competent to respond to vaccination. Cells required sufficient rest between stimulation events. Despite demonstrating the potential to expand the starting population at least 1040-fold, cells did not show loss of proliferation control and results were not due to contamination with young cells. Persistent stimulation by chronic infections or cancer can cause T cell proliferative senescence, functional exhaustion and death6. We found that although iterative acute stimulations also induced sustained expression and epigenetic remodelling of common exhaustion markers (including PD1, which is also known as PDCD1, and TOX) in the cells, they could still proliferate, execute antimicrobial functions and form quiescent memory cells. These observations provide a model to better understand memory cell differentiation, exhaustion, cancer and ageing, and show that functionally competent T cells can retain the potential for extraordinary population expansion and longevity well beyond their organismal lifespan.

DOI: 10.1038/s41586-022-05626-9

Source: https://www.nature.com/articles/s41586-022-05626-9

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html